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Sample records for experimental canine model

  1. Models of experimental saccular aneurysms of carotid arteries in canine

    International Nuclear Information System (INIS)

    Zhang Haixia; Cheng Yingsheng; Li Minghua

    2006-01-01

    Objective: To study the availability by making experimental saccular aneurysm models of carotid arteries in canine similar to human intracranial aneurysms. Methods: Twenty healthy canines with experimental saccular side-wall aneurysms of carotid arteries were created successfully by surgery. Results: Forty experimental saccular side-wall aneurysms of carotid arteries were created successfully with 36 aneurysms and parent arteries maintaining patency with each other and four spontaneously occluded confirmed by angiography. Model successful rate reached 90%. Conclusions: Experimental saccular side-wall aneurysms of carotid arteries in canines were one of best models created for simulating human intracranial aneurysms. (authors)

  2. Establishing experimental model of human internal carotid artery siphon segment in canine common carotid artery

    International Nuclear Information System (INIS)

    Cui Xuee; Li Minghua; Wang Yongli; Cheng Yingsheng; Li Wenbin

    2005-01-01

    Objective: To study the feasibility of establishing experimental model of human internal carotid artery siphon segment in canine common carotid artery (CCA) by end-to-end anastomoses of one side common carotid artery segment with the other side common carotid artery. Methods: Surgical techniques were used to make siphon model in 8 canines. One side CCA was taken as the parent artery and anastomosing with the cut off contra-lateral CCA segment which has passed through within the S-shaped glass tube. Two weeks after the creation of models angiography showed the model siphons were patent. Results: Experimental models of human internal carotid artery siphon segment were successfully made in all 8 dogs. Conclusions: It is practically feasible to establish experimental canine common carotid artery models of siphon segment simulating human internal carotid artery. (authors)

  3. The establishment of bilateral external iliac artery stenosis model in experimental canines and its angiographic evaluation

    International Nuclear Information System (INIS)

    Xia Yonghui; Li Weixiao; Bi Yonghua; Xu Ke

    2011-01-01

    Objective: To establish an experimental canine model of bilateral external iliac artery stenosis by surgical method with absorbable suture. Methods: Under general anesthesia bilateral external iliac arteries were partly obstructed (about 50%) with absorbable suture in ten dogs. Three months later angiography was performed to evaluate the arterial stricture degree. Results: Bilateral external iliac artery stenosis model was successfully established in eight dogs and the other two dogs died within two weeks after the procedure. Angiography performed three months after the procedure showed that the stricture degree of arterial lumen was (60.6±12.5)%. Conclusion: Satisfactory experimental canine model of bilateral external iliac artery stenosis can be established by surgical method with absorbable suture. This method can be used for reference when peripheral artery stenosis model is to be prepared in larger animals. (authors)

  4. Experimental study of pulmonary thromboembolism ischemia-reperfusion injury in canine model

    International Nuclear Information System (INIS)

    Li Jianjun; Zhai Renyou; Zhang Dongpo; Huang Qiang; Yu Ping; Dai Dingke; Bao Na

    2009-01-01

    Objective: To establish a canine model of pulmonary thromboembolism ischemia- reperfusion injury (PTE IRI) that may be used for imaging study. Methods: Ten male and 10 female healthy mongrel canines with (18.6±0.8) kg/body weight, were used. A Swan-Ganz catheter was introduced into the right internal jugular vein via a preset percutaneous sheath using the Seldinger technique, and then was with further insertion the pulmonary artery. Balloon occlusion of the right inferior lobe pulmonary artery for 4 hours was followed by removing the catheter and ending with 4 hours of reperfusion. CT was performed before ischemia, 4 h after ischemia and 4 h after reperfusion. At last, dogs were killed and the bilateral inferior lung tissues were prepared for the examination by light and electronic microscopy. Results: All canine models were successfully developed pulmonary thromboembolism ischemia-reperfusion injury. The examination of CT, light and electron microscopy consistently indicated the presence of permeability pulmonary edema after reperfusion. Conclusions: A closed-chest canine model in vivo of pulmonary thromboembolism ischemia-reperfusion injury can be established with virtual pathophysiological process in human and be as well as for imaging experimental study. (authors)

  5. A novel device for the occlusion of left atrial appendage: an experimental study in canine models

    International Nuclear Information System (INIS)

    Yang Zhihong; Qin Yongwen; Wu Hong; Hu Jianqiang; Wang Shengqiang; Ding Zhongru; Liu Zongjun

    2011-01-01

    Objective: To evaluate the feasibility, safety and biocompatibility of a novel device designed by the authors for the occlusion of left atrial appendage (LAA) in canine models. Methods: The occlusion of LAA was performed in 20 experimental dogs by using a novel LAA occluder, which was delivered to the LAA through a transseptal catheter. During the period of 2 weeks to 6 months after the procedure, the dogs were kept under observation for the device healing, migration, perforation and the formation of thrombus. Both scanning electron microscope (SEM) and transmission electron microscope (TEM) were used to examine the endothelial growth on the surface of the occluder and the structure of the endothelial cells. Results: Of the total 20 dogs, the novel device was successfully implanted in 14. The LAA was occluded completely in 13 dogs. No mobile thrombi caused by the implantation procedure were observed. Endothelialization of the atrium-facing surface was observed at one month after the procedure, and the surface was completely covered with endothelial cells at 3 months after the treatment, which was confirmed by gross, histological and SEM examinations. TEM examination showed that the structure of endothelial cells, the mitochondrion and sarcomere of atrial cardiocyte were all normal. Gross and light microscopic examination of the kidney, lung spleen and liver showed that there was no evidence of embolism or infarction. Conclusion: The novel device is safe and feasible for the occlusion of the LAA in experimental dogs. Further study is needed to observe its long-term safety. (authors)

  6. An experimental in-vivo canine model for adult shunt infection

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    Procop Gary

    2008-10-01

    Full Text Available Abstract Background Detailed human studies of the mechanisms and development of shunt infection in real time are not possible, and we have developed a canine hydrocephalus model to overcome this. The intention of this pilot study was to show that the canine hydrocephalus model could be shunted using conventional "human" shunts, and that a shunt infection could be established so that further studies could then be planned. Methods Hydrocephalus was induced in seven dogs (Canis familiaris by fourth ventricle obstruction. Four weeks later they were shunted using a Hakim Precision valve. Four of the dogs received shunts whose ventricular catheter had been inoculated with Staphylococcus epidermidis, and three were uninoculated controls. Four weeks after shunting the dogs were sacrificed and necropsy was performed. Removed shunts and tissue samples were examined microbiologically and isolates were subjected to detailed identification and genomic comparison. Results All the dogs remained well after shunting. Examination of removed shunt components revealed S. epidermidis in the brain and throughout the shunt system in the four inoculated animals, but in two of these Staphylococcus intermedius was also found. S. intermedius was also isolated from all three "negative" controls. There were slight differences between S. intermedius strains suggesting endogenous infection rather than cross- infection from a point source. Conclusion Shunt infection was established in the canine model, and had the experiment been extended beyond four weeks the typical microbiological, pathological and clinical features might have appeared. The occurrence of unplanned shunt infections in control animals due to canine normal skin flora reflects human clinical experience and underlines the usual source of bacteria causing shunt infection.

  7. Experimental studies on canine terminal carotid arterial aneurysm models pre- and post-embolized with microcoil

    International Nuclear Information System (INIS)

    Wang Qihong; Zhou Liangfu; Gong Jianqiu; Dai Jianhua; Zhang Xiaojun; Zhang Xinyuan

    2005-01-01

    Objective: To establish canine terminal saccular aneurysm model of common carotid artery (CCA), and evaluate the images and hemodynamic changes of aneurysm cavities pre- and post-embolized with microcoil (MC). Methods: Seven CCA terminal saccular aneurysm models had been created by using improved microsurgical technique. Seven to fourteen days after surgery, models were undergone color Doppler, Magnetic resonance image (MRI), Magnetic resonance angiography (MRA), digital subtraction angiography (DSA), and then the analysis of computational fluid dynamics (CFD) on these animal models were conducted. Afterwards they were compactly packed with MC, and then aneurysms again were examed under these methods, and simulation of pathological changes. Results: Models were created successfully with good MC compactly pack aneurysm cavities. DSA combined with other imaging methods can improve the diagnosis of aneurysms completely. CFD models can show the imitation hemodynamics of canine carotid aneurysms. Conclusions: This kind of aneurysm model is an ideal one on the area for the research of aneurysm embolization. Non-DSA imaging examination can noninvasively, repeatedly, clearly evaluate aneurysms pre- and post-embolized with MC. The interference on the inflow zone of the aneurysm is an effective method for cure and preventing recurrence of aneurysms. (authors)

  8. Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus.

    Science.gov (United States)

    da Fontoura Budaszewski, Renata; von Messling, Veronika

    2016-10-11

    Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the Canine distemper virus (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the Measles virus (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development.

  9. A newly-designed temporary cardia stent for the treatment of achalasia:an experimental study in canine models

    International Nuclear Information System (INIS)

    Kuang Xiaochun; Cheng Yingsheng; Zhu Yueqi; Li Feng; Wang Weiguo

    2010-01-01

    Objective: To assess the efficacy and safety of a newly-designed temporary covered cardia stent for the treatment of achalasia in canine models and to investigate the histopathological changes at different points of follow-up time after the stent was removed. Methods: The canine achalasia model was created by injecting benzyl-dimethyl-tetradecyl ammonium chloride (BAC) circumferentially into the lower esophageal sphincter (LES) of the dogs. Twenty-four dogs with achalasia were randomly and equally divided into two groups with 12 dogs in each group: control group (using routine esophageal stents) and study group (using newly-designed temporary covered cardia stents). Under fluoroscopic guidance stents were implanted in the esophagus and were taken away from the esophagus 4 days after stent insertion in experimental dogs of both groups. LES pressures and timed barium esophagography (TBE) were performed in all dogs before and immediately after the stenting procedure, as well as at one week, 3 and 6 months after the stent was removed. Every three dogs were sacrificed each time at one week, 3 and 6 months after the stent was removed. The esophageal cardia was excised and sent for pathological examination. Results: All animals well tolerated the stent insertion / removal and the follow-up procedures. No severe complications such as esophageal perforation occurred. Comparison between two groups showed that stent migration occurrence was much lower in study group (n = 1) than that in control group (n = 5). The reduction of LES pressures in study group was more significant in comparison with control group (at 6-month follow-up, P = 0.027). The difference in barium column product (height x width) between 0-min and 5-min TBE was statistically significant in study group (at 3-month follow-up, P = 0.009). Integrated analysis of multi-comparison for LES pressures among subgroups of each group revealed that the dogs in study group exhibited better outcomes than the dogs in

  10. A new experimental carotid siphon aneurysm model in canine based on the MR angiography and rapid prototyping technology

    International Nuclear Information System (INIS)

    Xie Jian; Li Minghua; Tan Huaqiao; Zhu Yueqi; Hu Dingjun; Qiao Ruihua; Fan Chunhua

    2009-01-01

    Objective: The aim of the experiment is to make an intracranial aneurysm model in canine. Methods: A digital tube was made based on raw magnetic resonance images of the human intracranial carotid artery. Then 6 tubes were made in the 3D rapid prototyping machine and coated with silicone. Finally we isolated the common carotid arteries of 6 canines and made them go through the tubes and anastomosed them end-to-side to get the aneurysm model. Six stents were implanted after one week. Results: Six aneurysm models were successfully made in canines. The parent artery had similar geometry of the human carotid siphon. All the aneurysms and parent arteries were patent in one week's follow-up. One canine died of excessive anesthesia after stenting. Two vascular models kept patent in one month without stenosis. The other 3 had some stenosis on the bends of the vessel. Conclusions: The aneurysm model in the experiment has high flexibility and reliability. The model provides an effective tool for research and testing neurovascular devices. It's also a useful device to train the neuroradiologists and interventional physicians. (authors)

  11. Influence of paclitaxel-eluting expandable metallic stent on tissue hyperplasia: an experimental study in a canine tracheal model

    International Nuclear Information System (INIS)

    Shin, Ji Hoon; Kim, Jung Sun; Kim, Tae Hyung; Kim, Eun Young; Choi, Won Chan; Woo, Chul Woong; Di, Zhenhai; Song, Ho Young; Yuk, Soon Hong; Lee, Yong Seok

    2005-01-01

    To evaluate the efficacy of a paclitaxel-eluting expandable metallic stent in reducing tissue hyperplasia following stent placement in a canine tracheal model. Nine paclitaxel-eluting stents (drug stent, DS) consisting of a proximal bare part and a distal polyurethane-covered part were placed in the trachea of nine dogs and nine control stents (control stent, CS) were placed in the other nine dogs. The dogs were scheduled to be sacrificed 12 weeks after stent placement. Gross and histological factors, such as epithelial erosion/ulcer, granulation tissue thickness and inflammatory cell infiltration were evaluated after each dog was sacrificed. There were no procedure-related complications or malpositioning of any of the stents. One CS migrated less than eight weeks following stent placement. Four dogs (one DS and three CS dogs) died between three and five weeks following stent placement. Therefore, pathologic specimens were obtained from eight DS and five CS dogs. Epithelial erosion/ulcer or inflammatory cell infiltration was slightly more prominent in the DS cases than in the CS cases, in both the bare part and the covered part. However, the data was not statistically significant. Granulation tissue thickness was lower in the DS cases than in the CS cases in both the bare part (mean, 3.63-mm vs. 4.37-mm) and the covered part (mean, 1.75-mm vs. 2,78 mm), but the data was also statistically insignificant. Although the data was not statistically significant, placement of paclitaxel-eluting expandable metallic stent demonstrates a tendency toward a decrease in granulation tissue thickness in canine tracheal models

  12. Influence of paclitaxel-eluting expandable metallic stent on tissue hyperplasia: an experimental study in a canine tracheal model

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ji Hoon; Kim, Jung Sun; Kim, Tae Hyung; Kim, Eun Young; Choi, Won Chan; Woo, Chul Woong; Di, Zhenhai; Song, Ho Young [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yuk, Soon Hong [Hannam University, College of Engineering, Daejeon (Korea, Republic of); Lee, Yong Seok [Wonkwang University College of Medicine, Iksan (Korea, Republic of)

    2005-07-15

    To evaluate the efficacy of a paclitaxel-eluting expandable metallic stent in reducing tissue hyperplasia following stent placement in a canine tracheal model. Nine paclitaxel-eluting stents (drug stent, DS) consisting of a proximal bare part and a distal polyurethane-covered part were placed in the trachea of nine dogs and nine control stents (control stent, CS) were placed in the other nine dogs. The dogs were scheduled to be sacrificed 12 weeks after stent placement. Gross and histological factors, such as epithelial erosion/ulcer, granulation tissue thickness and inflammatory cell infiltration were evaluated after each dog was sacrificed. There were no procedure-related complications or malpositioning of any of the stents. One CS migrated less than eight weeks following stent placement. Four dogs (one DS and three CS dogs) died between three and five weeks following stent placement. Therefore, pathologic specimens were obtained from eight DS and five CS dogs. Epithelial erosion/ulcer or inflammatory cell infiltration was slightly more prominent in the DS cases than in the CS cases, in both the bare part and the covered part. However, the data was not statistically significant. Granulation tissue thickness was lower in the DS cases than in the CS cases in both the bare part (mean, 3.63-mm vs. 4.37-mm) and the covered part (mean, 1.75-mm vs. 2,78 mm), but the data was also statistically insignificant. Although the data was not statistically significant, placement of paclitaxel-eluting expandable metallic stent demonstrates a tendency toward a decrease in granulation tissue thickness in canine tracheal models.

  13. Bioeffects of albumin-encapsulated microbubbles and real-time myocardial contrast echocardiography in an experimental canine model

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    P.M.M. Dourado

    2006-06-01

    Full Text Available Myocardial contrast echocardiography has been used for assessing myocardial perfusion. Some concerns regarding its safety still remain, mainly regarding the induction of microvascular alterations. We sought to determine the bioeffects of microbubbles and real-time myocardial contrast echocardiography (RTMCE in a closed-chest canine model. Eighteen mongrel dogs were randomly assigned to two groups. Nine were submitted to continuous intravenous infusion of perfluorocarbon-exposed sonicated dextrose albumin (PESDA plus continuous imaging using power pulse inversion RTMCE for 180 min, associated with manually deflagrated high-mechanical index impulses. The control group consisted of 3 dogs submitted to continuous imaging using RTMCE without PESDA, 3 dogs received PESDA alone, and 3 dogs were sham-operated. Hemodynamics and cardiac rhythm were monitored continuously. Histological analysis was performed on cardiac and pulmonary tissues. No hemodynamic changes or cardiac arrhythmias were observed in any group. Normal left ventricular ejection fraction and myocardial perfusion were maintained throughout the protocol. Frequency of mild and focal microhemorrhage areas in myocardial and pulmonary tissue was similar in PESDA plus RTMCE and control groups. The percentages of positive microscopical fields in the myocardium were 0.4 and 0.7% (P = NS in the PESDA plus RTMCE and control groups, respectively, and in the lungs they were 2.1 and 1.1%, respectively (P = NS. In this canine model, myocardial perfusion imaging obtained with PESDA and RTMCE was safe, with no alteration in cardiac rhythm or left ventricular function. Mild and focal myocardial and pulmonary microhemorrhages were observed in both groups, and may be attributed to surgical tissue manipulation.

  14. Influence of a dexamethasone-eluting covered stent on tissue reaction: an experimental study in a canine bronchial model

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ji Hoon; Song, Ho-Young; Choi, Gi Bok; Kim, Tae-Hyung; Suh, Ji-Yeon [University of Ulsan College of Medicine, Department of Radiology, Asan Medical Center, Seoul (Korea); Seo, Tae-Seok [Gachon Medical School, Department of Radiology, Gil Medical Center, Inchon (Korea); Yuk, Soon Hong [Hannam University, Department of Polymer Science and Engineering, College of Engineering, Daejeon (Korea); Kim, Young-Hwa [Soonchunhyang University Chonan Hospital, Department of Radiology, Chonan (Korea); Cho, Yong-Mee [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea)

    2005-06-01

    This study was designed to evaluate the feasibility and efficacy of a dexamethasone (DXM)-eluting, covered, self-expanding metallic stent to reduce tissue reaction following stent placement in a canine bronchial model. We placed a DXM-eluting, polyurethane-covered, self-expanding metallic stent (drug stent, DS) and a polyurethane-covered, self-expanding metallic stent (control stent, CS) alternately in each left main bronchus and left lower lobe bronchus in 12 dogs. The stents were 20 mm in diameter and length when fully expanded. The dose of DXM was approximately 36.7 mg in each DS, but was absent in the CS. The dogs were euthanased 1 week (n=4), 2 weeks (n=4) or 4 weeks (n=4) after stent placement. Histologic findings, such as epithelial erosion/ulcer or granulation tissue thickness, were obtained from the mid-portion of the bronchus, where the stent had been placed, and evaluated between DS and CS. There were no procedure-related complications or malpositioning of any of the bronchial stents. Stent migration was detected in one dog just before euthanasia 1 week following stent placement. Stent patency was maintained until euthanasia in all dogs. Epithelial erosion/ulcer (%) was significantly less in the DS (mean{+-}standard deviation, 46.88{+-}23.75) than in the CS (73.75{+-}14.08) (P=0.026) for all time-points. There was a decrease in epithelial erosion/ulcer as the follow-up period increased in both DS and CS. The granulation tissue thickness (mm) was less in DS (2.63{+-}2.05) than in CS (3.49{+-}2.95), although the difference was not significant (P=0.751) for all time-points. There was a tendency toward an increase in granulation tissue thickness and chronic lymphocytic infiltration as the follow-up period increased in both DS and CS. In conclusion, DXM-eluting, covered, self-expanding metallic stent seems to be effective in reducing tissue reaction secondary to stent placement in a canine bronchial model. (orig.)

  15. Influence of a dexamethasone-eluting covered stent on tissue reaction: an experimental study in a canine bronchial model

    International Nuclear Information System (INIS)

    Shin, Ji Hoon; Song, Ho-Young; Choi, Gi Bok; Kim, Tae-Hyung; Suh, Ji-Yeon; Seo, Tae-Seok; Yuk, Soon Hong; Kim, Young-Hwa; Cho, Yong-Mee

    2005-01-01

    This study was designed to evaluate the feasibility and efficacy of a dexamethasone (DXM)-eluting, covered, self-expanding metallic stent to reduce tissue reaction following stent placement in a canine bronchial model. We placed a DXM-eluting, polyurethane-covered, self-expanding metallic stent (drug stent, DS) and a polyurethane-covered, self-expanding metallic stent (control stent, CS) alternately in each left main bronchus and left lower lobe bronchus in 12 dogs. The stents were 20 mm in diameter and length when fully expanded. The dose of DXM was approximately 36.7 mg in each DS, but was absent in the CS. The dogs were euthanased 1 week (n=4), 2 weeks (n=4) or 4 weeks (n=4) after stent placement. Histologic findings, such as epithelial erosion/ulcer or granulation tissue thickness, were obtained from the mid-portion of the bronchus, where the stent had been placed, and evaluated between DS and CS. There were no procedure-related complications or malpositioning of any of the bronchial stents. Stent migration was detected in one dog just before euthanasia 1 week following stent placement. Stent patency was maintained until euthanasia in all dogs. Epithelial erosion/ulcer (%) was significantly less in the DS (mean±standard deviation, 46.88±23.75) than in the CS (73.75±14.08) (P=0.026) for all time-points. There was a decrease in epithelial erosion/ulcer as the follow-up period increased in both DS and CS. The granulation tissue thickness (mm) was less in DS (2.63±2.05) than in CS (3.49±2.95), although the difference was not significant (P=0.751) for all time-points. There was a tendency toward an increase in granulation tissue thickness and chronic lymphocytic infiltration as the follow-up period increased in both DS and CS. In conclusion, DXM-eluting, covered, self-expanding metallic stent seems to be effective in reducing tissue reaction secondary to stent placement in a canine bronchial model. (orig.)

  16. Multi-body simulation of a canine hind limb: model development, experimental validation and calculation of ground reaction forces

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    Wefstaedt Patrick

    2009-11-01

    Full Text Available Abstract Background Among other causes the long-term result of hip prostheses in dogs is determined by aseptic loosening. A prevention of prosthesis complications can be achieved by an optimization of the tribological system which finally results in improved implant duration. In this context a computerized model for the calculation of hip joint loadings during different motions would be of benefit. In a first step in the development of such an inverse dynamic multi-body simulation (MBS- model we here present the setup of a canine hind limb model applicable for the calculation of ground reaction forces. Methods The anatomical geometries of the MBS-model have been established using computer tomography- (CT- and magnetic resonance imaging- (MRI- data. The CT-data were collected from the pelvis, femora, tibiae and pads of a mixed-breed adult dog. Geometric information about 22 muscles of the pelvic extremity of 4 mixed-breed adult dogs was determined using MRI. Kinematic and kinetic data obtained by motion analysis of a clinically healthy dog during a gait cycle (1 m/s on an instrumented treadmill were used to drive the model in the multi-body simulation. Results and Discussion As a result the vertical ground reaction forces (z-direction calculated by the MBS-system show a maximum deviation of 1.75%BW for the left and 4.65%BW for the right hind limb from the treadmill measurements. The calculated peak ground reaction forces in z- and y-direction were found to be comparable to the treadmill measurements, whereas the curve characteristics of the forces in y-direction were not in complete alignment. Conclusion In conclusion, it could be demonstrated that the developed MBS-model is suitable for simulating ground reaction forces of dogs during walking. In forthcoming investigations the model will be developed further for the calculation of forces and moments acting on the hip joint during different movements, which can be of help in context with the in

  17. Embolus radiolabelling in a new canine model

    International Nuclear Information System (INIS)

    Kaufman, H.H.; Huchton, J.D.; Woo, J.; Cannon, D.C.; Anderson, J.H.

    1980-01-01

    Embolus radiolabelling with 131 I fibrinogen was studied in a canine model of internal carotid artery embolization. The dog was chosen as the experimental animal because of its maxillocarotid artery which permits collateral flow round the occlusion and helps to prevent strokes. Clot was prepared by incubating blood at room temperature to inactivate plasminogen activators and then refrigerating it to promote clot retraction. Emboli persisting 48 hours were seen in 80% of animals. Major strokes were not seen when 0.25 to 0.30 cm 3 were used. Autoradiography and well counting revealed uptake of isotope. The test, when refined, should provide a tool for the investigation of thromboemboli. (author)

  18. The short and long term effects of intraoperative electron beam radiotherapy (IORT) on thoracic organs after pneumonectomy an experimental study in the canine model

    NARCIS (Netherlands)

    de Boer, Willem; Mehta, DM; Timens, W; Hoekstra, HJ

    1999-01-01

    Purpose: The tolerance of mediastinal structures and thoracic organs to intraoperative radiotherapy (IORT) was investigated in the canine model. Methods and Materials: Twenty-two adult beagles divided into three groups were subjected to a left pneumonectomy and IORT (10 MeV electrons) at doses of 20

  19. Effect of the Plasmid-DNA Vaccination on Macroscopic and Microscopic Damage Caused by the Experimental Chronic Trypanosoma cruzi Infection in the Canine Model

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    Olivia Rodríguez-Morales

    2013-01-01

    Full Text Available The dog is considered the main domestic reservoir for Trypanosoma cruzi infection and a suitable experimental animal model to study the pathological changes during the course of Chagas disease (CD. Vaccine development is one of CD prevention methods to protect people at risk. Two plasmids containing genes encoding a trans-sialidase protein (TcSP and an amastigote-specific glycoprotein (TcSSP4 were used as DNA vaccines in a canine model. Splenomegaly was not found in either of the recombinant plasmid-immunized groups; however, cardiomegaly was absent in animals immunized only with the plasmid containing the TcSSP4 gene. The inflammation of subendocardial and myocardial tissues was prevented only with the immunization with TcSSP4 gene. In conclusion, the vaccination with these genes has a partial protective effect on the enlargement of splenic and cardiac tissues during the chronic CD and on microscopic hearth damage, since both plasmids prevented splenomegaly but only one avoided cardiomegaly, and the lesions in heart tissue of dog immunized with plasmid containing the TcSSP4 gene covered only subepicardial tissue.

  20. Experimental Model of Gene Transfection in Healthy Canine Myocardium: Perspectives of Gene Therapy for Ischemic Heart Disease

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    Renato A. K. Kalil

    2002-09-01

    Full Text Available OBJECTIVE: To assess the transfection of the gene that encodes green fluorescent protein (GFP through direct intramyocardial injection. METHODS: The pREGFP plasmid vector was used. The EGFP gene was inserted downstream from the constitutive promoter of the Rous sarcoma virus. Five male dogs were used (mean weight 13.5 kg, in which 0.5 mL of saline solution (n=1 or 0.5 mL of plasmid solution containing 0.5 µg of pREGFP/dog (n=4 were injected into the myocardium of the left ventricular lateral wall. The dogs were euthanized 1 week later, and cardiac biopsies were obtained. RESULTS: Fluorescence microscopy showed differences between the cells transfected and not transfected with pREGFP plasmid. Mild fluorescence was observed in the cardiac fibers that received saline solution; however, the myocardial cells transfected with pREGFP had overt EGFP expression. CONCLUSION: Transfection with the EGFP gene in healthy canine myocardium was effective. The reproduction of this efficacy using vascular endothelial growth factor (VEGF instead of EGFP aims at developing gene therapy for ischemic heart disease.

  1. Radioactive metallic stent for palliative treatment of esopageal cancer using Ho-166: an experimental study in canine model

    Energy Technology Data Exchange (ETDEWEB)

    Won, J. H.; Lee, J. D. [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of); Wang, H. J.; Lim, H. E.; Park, C. H. [College of Medicine, Ajou Univ., Inchon (Korea, Republic of); Park, K. B. [KAERI, Taejon (Korea, Republic of)

    1999-07-01

    Self-expandable metallic stents are widely used for palliative treatment of esophageal cancer, however, tumor overgrowth and short survaval limit its long-term effect. The purpose of this study is to evaluate tissue response of the radiation effect in normal canine esophagus whether metallic stents coated with radioactive H-166 is effective for patients survival and preservation of stent patency longer than stents without radioactive materials. Ho-166 was incorporated within polyurethan (50{mu}) and coated over the outer surface of self-expandable metallic stents. Metallic stents with radioactivity of 4.0-7.8mCi (Group A), 1.0-1.8 mCi (Group B) and 0.5-0.7mCi (Group C) were placed in normal mid-esophagus in twelve dogs (Group A), five (Group B) and another five dogs (Group C) respectively, and the stents were tightly anchored by surgery to prevent migration. Estimated radiation dose was 6-70 Gy in Group C. Fluoroscopy confirmed stents in esophagus without migration for at least two days. The dogs were sacrified at two or three months later and histopathologic examinations were performed. In group A, mid-esophagus stricture, mucosal ulceration were found in all specimens. Severe fibrosis and degeneration of muscular propria, upper one half were found in three and complete fibrosis of esophageal wall, however, esophageal perforation was found but muscular layer was intact. In group C, no histological changes was demonstrated in three but submucosal inflammation with intact mucosa in two. In therapeutic dose level (group B), radioactive metallic stent showed radiation effect within esophageal wall without complication which might give additional palliative effect in malignant espohageal stricture.

  2. Experimental tumor growth of canine osteosarcoma cell line on chick embryo chorioallantoic membrane (in vivo studies).

    Science.gov (United States)

    Walewska, Magdalena; Dolka, Izabella; Małek, Anna; Wojtalewicz, Anna; Wojtkowska, Agata; Żbikowski, Artur; Lechowski, Roman; Zabielska-Koczywąs, Katarzyna

    2017-05-12

    The chick embryo chorioallantoic membrane (CAM) model is extensively used in human medicine in preclinical oncological studies. The CAM model has several advantages: low cost, simple experimental approach, time saving and following "3R principles". Research has shown that the human osteosarcoma cell lines U2OS, MMNG-HOS, and SAOS can form tumors on the CAM. In veterinary medicine, this has been described only for feline fibrosarcomas, feline mammary carcinomas and canine osteosarcomas. However, in case of canine osteosarcomas, it has been shown that only non-adherent osteosarcoma stem cells isolated from KTOSA5 and CSKOS cell lines have the ability to form microtumors on the CAM after an incubation period of 5 days, in contrast to adherent KTOSA5 and CSKOS cells. In the presented study, we have proven that the commercial adherent canine osteosarcoma cell line (D-17) can form vascularized tumors on the CAM after the incubation period of 10 days.

  3. Laparoscopic radical prostatectomy in the canine model.

    Science.gov (United States)

    Price, D T; Chari, R S; Neighbors, J D; Eubanks, S; Schuessler, W W; Preminger, G M

    1996-12-01

    The purpose of this study was to determine the feasibility of performing laparoscopic radical prostatectomy in a canine model. Laparoscopic radical prostatectomy was performed on six adult male canines. A new endoscopic needle driver was used to construct a secure vesicourethral anastomosis. Average operative time required to complete the procedure was 304 min (range 270-345 min). Dissection of the prostate gland took an average of 67 min (range 35-90 min), and construction of the vesicourethral anastomosis took 154 min (rage 80-240 min). There were no intraoperative complications and only one postoperative complication (anastomotic leak). Five of the six animals recovered uneventfully from the procedure, and their foley catheters were removed 10-14 days postoperatively after a retrograde cystourethrogram demonstrated an intact vesicourethral anastomosis. Four (80%) of the surviving animals were clinically continent within 10 days after catheter removal. Post mortem examination confirmed that the vesicourethral anastomosis was intact with no evidence of urine extravasation. These data demonstrate the feasibility of laparoscopic radical prostatectomy in a canine model, and suggest that additional work with this technique should be continued to develop its potential clinical application.

  4. Evaluation of the efficacy and duration of immunity of a canine combination vaccine against virulent parvovirus, infectious canine hepatitis virus, and distemper virus experimental challenges.

    Science.gov (United States)

    Abdelmagid, Omar Y; Larson, Laurie; Payne, Laurie; Tubbs, Anna; Wasmoen, Terri; Schultz, Ronald

    2004-01-01

    The results of this study confirmed that dogs vaccinated subcutaneously with a commercially available multivalent vaccine containing modified-live canine distemper virus, canine adenovirus type 2, canine parvovirus type 2b, and canine parainfluenza virus antigens were protected against sequential experimental challenge 55 to 57 months after initial vaccination given at 7 to 8 weeks of age. All 10 vaccinates were protected against clinical diseases and mortality following parvovirus and infectious canine hepatitis experimental infections. All vaccinates were protected against mortality and 90% against clinical disease following distemper challenge. These data support at least a 4-year duration of immunity for these three "core" fractions in the combination vaccine.

  5. The experimental study of 32P and diallyl trisulfide coating stent for inhibiting neointimal hyperplasia in a canine model of coronary restenosis

    International Nuclear Information System (INIS)

    Xu Shanghua; Jiang Hong; Li Gengshan; Jiang Xuejun; Li Xiaoyan; Chen Yuanxiu; Wang Hairong; Wu Kegui; Nie Xiaomin

    2004-01-01

    Objective: To assesses the efficiency of 32 P and diallyl trisulfide (DT)-coated coronary stents on neointimal proliferation in a canine model of restenosis. Methods: 32 P (740 kBq/stent), DT (210 μg/stent) alone and jointly coated stents were deployed with mild oversizing in both the left circumflex coronary artery (LCX) and the left anterior descending coronary artery (LAD) of 10 dogs. The implantation of protein-coated stents was used as the control. The therapeutic effect was assessed 6 months after the intervention. The dogs were sacrificed and the vessels were excised. For morphologic examinations the tissue sections were stained with HE and Van Gieson. Results: Compared with the control stents, the neointimal area reduced in stents coated with 32 P, DT alone and 32 P+DT [ 32 P: (2.63±0.48) mm 2 , DT: (2.50±0.49) mm 2 , 32 P+DT: (1.42±0.41) mm 2 vs control group: (4.87±0. 80) mm 2 , P=0.001]. 32 P+DT was more effective than either of them alone for reducing the neointimal area (P≤0.005). Both jointly and alone coated stents of 32 P, DT decreased the percent area stenosis [ 32 P: (32.48±4.79)%, DT: (30.04±5.43)%, 32 P+DT: (17.21±4.05)% vs control group: (54.62±6.82)%, P 32 P+DT group compared with 32 P or DT-coated stents group (P≤0.001). Angiographic restenosis (diameter stenosis) was lighter in stents coated with 32 P, DT and 32 P+DT compared with control stents (P 32 P+DT was more effective than 32 P or DT alone for reducing diameter stenosis (P≤0.005). No evidence of 'edge effect' was seen in adjacent, nonstented coronary segments. Conclusion: Coronary stents coated with 32 P plus DT produced a significantly reduced neointimal hyperplasia and restenosis rate in the canine LCX and LAD 6 months after stents implantation

  6. Experimental chemonucleolysis with chymopapain in canine intervertebral disks

    International Nuclear Information System (INIS)

    Kudo, T.; Sumi, A.; Hashimoto, A.

    1993-01-01

    The present study describes the radiological and histological changes in the canine intervertebral disk after the experimental injection of chymopapain as the chemical reagent, and determines the appropriate dose of the enzyme for treatment of herniated disks. By radiography, narrowing of the disk space was observed within 2 weeks after the injection of chymopapain, and recovered to 74.1% in the 0.1 mg group, 61.1% in the 1.0 mg group and 71.7% in the 10.0 mg group at 12 weeks. The disk space recovery showed a tendency to delay with aging. Microscopically, proteoglycan positive matrix appeared and the nuclear space was reduced in each disk at 2 weeks after chymopapain injection. The nucleus pulposus contained an irregularly-defined mass consisting of clusters of degenerated notochordal cells surrounded by proliferated chondrocytes and collagen matrix. In each disk at 12 weeks after chymopapain injection, the center of the nucleus pulposus was replaced by fibrocartilage tissue. In the disk into which 10.0 mg chymopapain was injected, the nuclear space filled with dense fibrocartilage tissue without a regenerated matrix component and narrowing of the disk were maintained. It is suggested that canine chemonucleolysis with 10.0 mg of chymopapain reduces the interdiskal pressure. This treatment may therefore relieve the signs and symptoms of herniation of the nucleus pulposus, and may effect chemical disk decompression

  7. Investigation of the correlation of serum IL-31 with severity of dermatitis in an experimental model of canine atopic dermatitis using beagle dogs.

    Science.gov (United States)

    Marsella, Rosanna; Ahrens, Kim; Sanford, Rachel

    2018-02-01

    IL-31 is a cytokine that is believed to play an important role in atopic dermatitis (AD). IL-31 levels positively correlate with disease severity in children with AD. Currently, there is no study that has investigated such a correlation in atopic dogs. The purpose of this study was to evaluate the correlation between IL-31 serum levels and severity of dermatitis. It was hypothesized that a positive correlation exists between severity of AD and circulating levels of IL-31. Sixteen atopic beagles experimentally sensitized to house dust mites. Atopic beagles were exposed to dust mites epicutaneously twice weekly for four weeks. Severity of dermatitis was scored by the Canine Atopic Dermatitis and Extent Severity Index, 3 rd iteration (CADESI-03) on days 0 and 28. Blood samples were taken on days 0 and 28 to measure serum IL-31 using a commercially available ELISA. Correlation between CADESI-03 scores and serum IL-31 levels was not detected on day 0 (Pearson, r = -0.2609, P = 0.3291). After flare-up of dermatitis was induced with allergen exposure, a significant positive correlation was detected between serum IL-31 and CADESI-03 on Day 28 (r = 0.6738, P = 0.004). Positive correlation was detected in active disease between severity of dermatitis and circulating levels of IL-31. Additional studies are needed to investigate this correlation in other breeds of dogs and to test whether circulating levels of IL-31 may predict clinical response to biological agents aimed at IL-31. © 2017 ESVD and ACVD.

  8. The short and long term effects of intraoperative electron beam radiotherapy (IORT) on thoracic organs after pneumonectomy an experimental study in the canine model

    International Nuclear Information System (INIS)

    Boer, Willem J. de; Mehta, Dinesh M.; Timens, Wim; Hoekstra, Harald J.

    1999-01-01

    Purpose: The tolerance of mediastinal structures and thoracic organs to intraoperative radiotherapy (IORT) was investigated in the canine model. Methods and Materials: Twenty-two adult beagles divided into three groups were subjected to a left pneumonectomy and IORT (10 MeV electrons) at doses of 20 Gy (n = 9), 25 Gy (n = 4), or 30 Gy (n = 9). Intraoperative electron beam radiotherapy was delivered through a 5 cm circular lucite cone encompassing a mediastinal field including the bronchial stump, aorta, esophagus, heart, phrenic nerve, contralateral hilar structures, and lung. Clinical monitoring was performed with regular chest X-ray, ECG, bronchoscopy, esofagoscopy, and fluoroscopy. From the different treatment dose groups, dogs were electively sacrificed at 1.5, 6, 12, and 72 months with complete autopsies. Results: There was no bronchial stump dehiscence or acute morbidity. Four dogs developed radiation induced esophagitis (18%), one in the 20 Gy IORT group (11%) and three in the 30 Gy IORT group (33%). There were six IORT related mortalities (27.5%), one esophagoaortic fistula (4.5%) and five bronchovascular fistulas (23%): two in the 20 Gy IORT group (22%), two in the 25 Gy IORT group (50%) and two in the 30 Gy IORT group (22%). Histopathological findings in uncomplicated follow-up showed marked myointimal fibrosis in the muscular arteries, submucosal fibrosis of the esophagus, and interstitial fibrosis of bronchial and lung tissue, especially in the higher dose group. Conclusion: The mediastinal vascular, bronchial and esophageal structures are relatively sensitive to doses > 20Gy IORT. The IORT related morbidity found in this study may be lower when the current clinically used IORT doses of 10-15 Gy are applied. Further clinical application of IORT in the future treatment strategies for resectable non small cell lung cancer may be worthwhile to investigate

  9. Experimental study of a closed-chest pulmonary embolism-reperfusion injury canine model by means of Swan-Ganz catheter

    International Nuclear Information System (INIS)

    Bao Na; Zhai Renyou Jiang Tao; Wang Yajie; Zheng Juan; Wang Chen

    2007-01-01

    Objective: To establish a closed-chest pulmonary embolism-reperfusion animal model by Swan-Ganz catheter and to explore the mechanisms of pulmonary embolism (PE)-reperfusion injury (RI). Methods: Experiments were made on 14 mongrel dogs, ranging in weight from 15 to 18 kg, anesthetized with 3% pentobarbital sodium. The dogs were intubated with I. D. 7 endotracheal tubes. Under sterile conditions, a 7 F Swan-Ganz catheter via the external jugular vein was positioned in the unilateral pulmonary diaphragmatic lobe (DL) artery. Occlusion/reperfusion of the DL artery was controlled with 1.2 ml diluted contrast agent filled into/drawn from the balloon. After the 24 h PE, the balloon was deflated to result in 4 h reperfusion of the DL. Measurements of blood gases and tumor necrosis factor-α (TNF-α)were made at normal condition, at 24 h PE and at 4 h reperfusion. Thin-section CT scans were performed at normal condition, 24 h PE, 30 rain, 1, 2, 3 and 4 h reperfusion, respectively. At the end of each experiment, tissue specimens of bilateral diaphragmatic lobes were obtained for both wet/dry (W/D) weight ratio and for pathological study. Results: Reperfusion pulmonary edema (RPE) was an acute, mixed, noncardiogenic edema that was observed in all 14 dogs who had been successfully established as PE/RI animal models. RPE demonstrated heterogeneous ground-glass opacifications that predominated in the areas distal to the recanalized vessels. It manifested pathologically as an edematous lung infihrated by inflammatory cells. The mean of PaO 2 and TNF-α of 4 h reperfusion was (81 ± 4) mm Hg( 1 mm Hg =0.133 kPa) and (16.0 ± 2.5)pg/ml, which were significantly different (P<0.05) from normal value [(96 ± 6)mm Hg and (13.9 ± 2.0) pg/ml]. The W/D of the injured lung (6.3 ± 1.2) was significantly greater (P<0.01) than that of the contralateral lung (4.5 ± 1.2), suggesting that the increase in the lung water was due to reperfusion injury. Conclusion: The closed-chest canine model

  10. Duchenne Muscular Dystrophy Gene Therapy in the Canine Model

    Science.gov (United States)

    2015-01-01

    Abstract Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disease caused by dystrophin deficiency. Gene therapy has significantly improved the outcome of dystrophin-deficient mice. Yet, clinical translation has not resulted in the expected benefits in human patients. This translational gap is largely because of the insufficient modeling of DMD in mice. Specifically, mice lacking dystrophin show minimum dystrophic symptoms, and they do not respond to the gene therapy vector in the same way as human patients do. Further, the size of a mouse is hundredfolds smaller than a boy, making it impossible to scale-up gene therapy in a mouse model. None of these limitations exist in the canine DMD (cDMD) model. For this reason, cDMD dogs have been considered a highly valuable platform to test experimental DMD gene therapy. Over the last three decades, a variety of gene therapy approaches have been evaluated in cDMD dogs using a number of nonviral and viral vectors. These studies have provided critical insight for the development of an effective gene therapy protocol in human patients. This review discusses the history, current status, and future directions of the DMD gene therapy in the canine model. PMID:25710459

  11. Transcription of Toll-Like Receptors 2, 3, 4 and 9, FoxP3 and Th17 Cytokines in a Susceptible Experimental Model of Canine Leishmania infantum Infection

    Science.gov (United States)

    Hosein, Shazia; Rodríguez-Cortés, Alhelí; Blake, Damer P.; Allenspach, Karin; Alberola, Jordi; Solano-Gallego, Laia

    2015-01-01

    Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in

  12. Successful experimental challenge of dogs with canine parvovirus-2.

    OpenAIRE

    Carman, S; Povey, C

    1982-01-01

    Withholding food from dogs for 24 hours prior to, and for 48 hours following oral challenge with a gut mucosal homogenate of canine parvovirus-2, was a successful means of reproducing gastroenteric signs of canine parvovirus-2 infection. Twenty-one of 24 dogs, which had previously received various vaccine preparations of mink enteritis virus or were unvaccinated, and which were starved at challenge, developed soft or liquid feces with large or without large clots of mucus. Altered feces were ...

  13. Canine C-peptide for characterization of experimental diabetes in dogs

    International Nuclear Information System (INIS)

    Fischer, U.; Besch, W.; Freyse, E.-J.

    1985-01-01

    Radioimmunoassay of canine C-peptide (CCP) was developed for the characterization of endogenous beta cell function in experimentally diabetic dogs. The animals were rendered diabetic by subtotal pancreatectomy and intrasurgical infusion of 2 mg/kg streptozotocin into the superior pancreaticoduodenal artery. After an average duration of diabetes of 5 months the animals showed zero peripheral venous fasting CCP levels with no response to feeding, OGTT/i.v. glucagon loading or i.v. glucose tolerance testing. The data on CCP levels entirely coincided with simultaneously measured plasma IRI levels. In non-diabetic control animals clear-cut CCP increases were observed after all stimuli. The experimental model provided an IDDM-type diabetes without toxic symptoms but with a sufficient exocrine pancreatic function. The comparison showed that plasma IRI analyses would also allow reliable characterization of insulinogenic functions in these animals. (author)

  14. Experimental research of covered stent implanted in canine hepatic artery

    International Nuclear Information System (INIS)

    Zhou Bing; Liu Linxiang; Li Minghua; Wang Yongli; Cheng Yongde

    2007-01-01

    Objective: To evaluate the feasibility of success rate of implantation, post-procedure stenosis rate, apposition ability and endothelialization level, etc. for implantation with balloon-expandable covered stent in canine hepatic artery. Methods: 8 adult canines were implanted with balloon-expendable stents covered by expandable poly Teflon ester membrane (e-PTFEM). Follow-up DSA was performed immediately, 2, 4 and 12 wk after the procedure. The canines were sacrificed for histopathologic examination and statistical analysis with correlation of implantation manenvor and angiographic manifestations. Results: 8 cases were all implanted with the covered stents in proper hepatic artery/right hepatic artery successfully; showing good apposition ability and non-opacification of the separated branches. 2 cases showed intraluminal obvious stenosis( > 50%)of the stent at 2 weeks follow-up, so did 3 cases at 12 weeks follow-up, and the total stenosis rate was 37.5% and 5 cases manifested full endothelialization (3 different locations of the sample all manifested full endothelialization), 3 cased manifested partial endothelialization (at least 1 location of the sample didn't show full endothelialization), and the two terminal parts were easier to get endothelialization than the central part. Before and after the stent implantation, hepatic function of all cases didn't demonstrate any obvious changes. Conclusions: Balloon-expandable covered stent can be implanted in canine hepatic artery. successfully, with good apposition ability, full endothelialization, and no influence on hepatic function. (authors)

  15. Wound healing modulators in a tracheoplasty canine model.

    Science.gov (United States)

    Olmos-Zúñiga, J Raúl; Hernández-Jiménez, Claudia; Díaz-Martínez, Emmanuel; Jasso-Victoria, Rogelio; Sotres-Vega, Avelina; Gaxiola-Gaxiola, Miguel O; Villalba-Caloca, Jaime; Baltazares-Lipp, Matilde; Santillán-Doherty, Patricio; Santibáñez-Salgado, J Alfredo

    2007-01-01

    Postsurgical tracheal stenosis results from fibrosis formation due to ischemia. There are healing modulators, hyaluronic acid (HA) and collagen polyvinylpyrrolidone (CPVP), which reduce collagen fibers formation. Thus we can hypothesize that the topical application of one of these modulators can diminish postsurgical tracheal scarring and stenosis. The aim of this work was to evaluate the macroscopic, microscopic, and biochemical changes of tracheal healing after the application of HA or CPVP in a canine tracheoplasty model. The study design was prospective experimental investigation in a canine model. Eighteen mongrel dogs underwent three cervical tracheal rings resection and end-to-end anastomosis. They were randomized into three groups according to treatment: group I (control group) (n = 6), topical application of saline solution on tracheal anastomosis; group II (n = 6), topical application of 15 microg HA on tracheal anastomosis; and group III (n = 6), topical application of 2.5 mg CPVP on tracheal anastomosis. They were evaluated clinical, radiological and tracheoscopically during 4 weeks. They were euthanized at the end of the study time. Macroscopic, microscopic, and biochemical changes of tracheal anastomosis healing were analyzed. Collagen formation was quantified by the Woessner method. All the animals survived the surgical procedure and study period. Macroscopic, radiologic, and endoscopic studies showed that animals in group I developed tracheal stenosis, inflammation, and firm fibrous tissue formation, and histological studies also showed severe inflammatory reaction and fibrosis formation. Groups II (HA) and III (CPVP) showed well-organized thin collagen fibers with minimal inflammatory response. Biochemical evaluation revealed a higher collagen concentration in group I animals (analysis of variance [ANOVA] p anastomosis diminished the degree of stenosis and inflammatory reaction. Both modulators improved tracheal healing.

  16. Canine gastritis.

    Science.gov (United States)

    Webb, Craig; Twedt, David C

    2003-09-01

    Gastritis--inflammation of the stomach--is a frequently cited differential yet rarely characterized diagnosis in cases of canine anorexia and vomiting. Although the list of rule-outs for acute or chronic gastritis is extensive, a review of the veterinary literature reveals fewer than 15 articles that have focused on clinical cases of canine gastritis over the last 25 years. The dog frequently appears in the human literature as an experimentally manipulated model for the study of endoscopic techniques or the effect of medications on gastric mucosa. In the veterinary patient, cases of acute gastritis are rarely pursued with the complete diagnostic armamentarium, and cases of chronic gastritis are rarely found to occur as an entity isolated from the rest of the gastrointestinal tract. This article focuses on those findings most clinically relevant to cases of canine gastritis in veterinary medicine.

  17. Tissue engineering rib with the incorporation of biodegradable polymer cage and BMSCs/decalcified bone: an experimental study in a canine model.

    Science.gov (United States)

    Tang, Hua; Wu, Bin; Qin, Xiong; Zhang, Lu; Kretlow, Jim; Xu, Zhifei

    2013-05-20

    The reconstruction of large bone defects, including rib defects, remains a challenge for surgeons. In this study, we used biodegradable polydioxanone (PDO) cages to tissue engineer ribs for the reconstruction of 4cm-long costal defects. PDO sutures were used to weave 6cm long and 1cm diameter cages. Demineralized bone matrix (DBM) which is a xenograft was molded into cuboids and seeded with second passage bone marrow mesenchymal stem cells (BMSCs) that had been osteogenically induced. Two DBM cuboids seeded with BMSCs were put into the PDO cage and used to reconstruct the costal defects. Radiographic examination including 3D reconstruction, histologic examination and mechanical test was performed after 24 postoperative weeks. All the experimental subjects survived. In all groups, the PDO cage had completely degraded after 24 weeks and been replaced by fibrous tissue. Better shape and radian were achieved in PDO cages filled with DBM and BMSCs than in the other two groups (cages alone, or cages filled with acellular DBM cuboids). When the repaired ribs were subjected to an outer force, the ribs in the PDO cage/DBMs/BMSCs group kept their original shape while ribs in the other two groups deformed. In the PDO cage/DBMs/BMSCs groups, we also observed bony union at all the construct interfaces while there was no bony union observed in the other two groups. This result was also confirmed by radiographic and histologic examination. This study demonstrates that biodegradable PDO cage in combination with two short BMSCs/DBM cuboids can repair large rib defects. The satisfactory repair rate suggests that this might be a feasible approach for large bone repair.

  18. Targeting VEGF in canine oxygen-induced retinopathy - a model for human retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    McLeod DS

    2016-05-01

    Full Text Available D Scott McLeod, Gerard A Lutty Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD, USA Abstract: Development of the dog superficial retinal vasculature is similar to the mechanism of human retinal vasculature development; they both develop by vasculogenesis, differentiation, and assembly of vascular precursors called angioblasts. Canine oxygen-induced retinopathy (OIR was first developed by Arnall Patz in an effort to experimentally determine the effects of hyperoxia on the development of the retinal vasculature. The canine OIR model has many characteristics in common with human retinopathy of prematurity. Exposure of 1-day-old dogs to hyperoxia for 4 days causes a vaso-obliteration throughout the retina. Vasoproliferation, after the animals have returned to room air, is robust. The initial small preretinal neovascular formations anastomose to form large preretinal membranes that eventually cause tractional retinal folds. The end-stage pathology of the canine model is similar to stage IV human retinopathy of prematurity. Therefore, canine OIR is an excellent forum to evaluate the response to drugs targeting VEGF and its receptors. Evaluation of an antibody to VEGF-R2 and the VEGF-Trap demonstrated that doses should be titered down so that preretinal neovascularization is inhibited but retinal revascularization is able to proceed, vascularizing peripheral retina and preventing it from being a source of VEGF. Keywords: angioblasts, blood vessels, endothelial cells, oxygen, retinopathy, retina, vascular endothelial cell growth factor

  19. Targeting VEGF in canine oxygen-induced retinopathy - a model for human retinopathy of prematurity.

    Science.gov (United States)

    McLeod, D Scott; Lutty, Gerard A

    2016-01-01

    Development of the dog superficial retinal vasculature is similar to the mechanism of human retinal vasculature development; they both develop by vasculogenesis, differentiation, and assembly of vascular precursors called angioblasts. Canine oxygen-induced retinopathy (OIR) was first developed by Arnall Patz in an effort to experimentally determine the effects of hyperoxia on the development of the retinal vasculature. The canine OIR model has many characteristics in common with human retinopathy of prematurity. Exposure of 1-day-old dogs to hyperoxia for 4 days causes a vaso-obliteration throughout the retina. Vasoproliferation, after the animals have returned to room air, is robust. The initial small preretinal neovascular formations anastomose to form large preretinal membranes that eventually cause tractional retinal folds. The end-stage pathology of the canine model is similar to stage IV human retinopathy of prematurity. Therefore, canine OIR is an excellent forum to evaluate the response to drugs targeting VEGF and its receptors. Evaluation of an antibody to VEGF-R2 and the VEGF-Trap demonstrated that doses should be titered down so that preretinal neovascularization is inhibited but retinal revascularization is able to proceed, vascularizing peripheral retina and preventing it from being a source of VEGF.

  20. Stabilization of multiple rib fractures in a canine model.

    Science.gov (United States)

    Huang, Ke-Nan; Xu, Zhi-Fei; Sun, Ju-Xian; Ding, Xin-Yu; Wu, Bin; Li, Wei; Qin, Xiong; Tang, Hua

    2014-12-01

    Operative stabilization is frequently used in the clinical treatment of multiple rib fractures (MRF); however, no ideal material exists for use in this fixation. This study investigates a newly developed biodegradable plate system for the stabilization of MRF. Silk fiber-reinforced polycaprolactone (SF/PCL) plates were developed for rib fracture stabilization and studied using a canine flail chest model. Adult mongrel dogs were divided into three groups: one group received the SF/PCL plates, one group received standard clinical steel plates, and the final group did not undergo operative fracture stabilization (n = 6 for each group). Radiographic, mechanical, and histologic examination was performed to evaluate the effectiveness of the biodegradable material for the stabilization of the rib fractures. No nonunion and no infections were found when using SF-PCL plates. The fracture sites collapsed in the untreated control group, leading to obvious chest wall deformity not encountered in the two groups that underwent operative stabilization. Our experimental study shows that the SF/PCL plate has the biocompatibility and mechanical strength suitable for fixation of MRF and is potentially ideal for the treatment of these injuries. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Irradiation inhibits vascular anastomotic stenosis in a canine model

    International Nuclear Information System (INIS)

    Saito, Takeshi; Iguchi, Atsushi; Tabayashi, Koichi

    2009-01-01

    The graft patency rate after coronary artery bypass grafting (CABG) correlates with anastomotic stenosis. Intracoronary radiation therapy is effective for preventing restenosis after percutaneous coronary intervention (PCI). We postulated that intracoronary radiation therapy could prevent anastomotic stenosis and tested this hypothesis in an animal model. Femoral arteries and veins of beagle dogs were harvested, and composite arterioarterial and arteriovenous grafts were prepared. After external irradiation of the anastomotic sites, these composite grafts were transplanted into femoral arteries. Histomorphometric and immunohistological analyses of the anastomotic sites were performed. The study groups consisted of controls and animals exposed to 10 Gy, 20 Gy, and 30 Gy (n=5, in each group). In the artery graft model, the ratio of negative remodeling was significantly increased in all groups exposed to ≥10 Gy. The ratio of neointimal hyperplasia was significantly decreased in all groups exposed to ≥10 Gy. Cell density of anti-α-actin antibody-positive cells and anti-proliferating cell nuclear antigen (PCNA) antibody-positive cells was highest in the adventitial layer, and the density decreased as the dosage increased. Experimental results were almost the same in the vein graft models as in the artery graft models. With double immunohistostaining, the anti-PCNA antibody-positive cells expressed α-actin. Irradiation can inhibit anastomotic stenosis in a canine model. Adventitia is a factor in the creation of stenosis, and irradiation appears to target the adventitia. We speculate that there might be a possible role for intracoronary irradiation in the future to prevent anastomotic stenosis. (author)

  2. Construct canine intracranial aneurysm model by endovascular technique

    International Nuclear Information System (INIS)

    Liang Xiaodong; Liu Yizhi; Ni Caifang; Ding Yi

    2004-01-01

    Objective: To construct canine bifurcation aneurysms suitable for evaluating the exploration of endovascular devices for interventional therapy by endovascular technique. Methods: The right common carotid artery of six dogs was expanded with a pliable balloon by means of endovascular technique, then embolization with detached balloon was taken at their originations DAS examination were performed on 1, 2, 3 d after the procedurse. Results: 6 aneurysm models were created in six dogs successfully with the mean width and height of the aneurysms decreasing in 3 days. Conclusions: This canine aneurysm model presents the virtue in the size and shape of human cerebral bifurcation saccular aneurysms on DSA image, suitable for developing the exploration of endovascular devices for aneurismal therapy. The procedure is quick, reliable and reproducible. (authors)

  3. Canine intrahepatic vasculature: is a functional anatomic model relevant to the dog?

    Science.gov (United States)

    Hall, Jon L; Mannion, Paddy; Ladlow, Jane F

    2015-01-01

    To clarify canine intrahepatic portal and hepatic venous system anatomy using corrosion casting and advanced imaging and to devise a novel functional anatomic model of the canine liver to investigate whether this could help guide the planning and surgical procedure of partial hepatic lobectomy and interventional radiological procedures. Prospective experimental study. Adult Greyhound cadavers (n = 8). Portal and hepatic vein corrosion casts of healthy livers were assessed using computed tomography (CT). The hepatic lobes have a consistent hilar hepatic and portal vein supply with some variation in the number of intrahepatic branches. For all specimens, 3 surgically resectable areas were identified in the left lateral lobe and 2 surgically resectable areas were identified in the right medial lobe as defined by a functional anatomic model. CT of detailed acrylic casts allowed complex intrahepatic vascular relationships to be investigated and compared with previous studies. Improving understanding of the intrahepatic vascular supply facilitates interpretation of advanced images in clinical patients, the planning and performance of surgical procedures, and may facilitate interventional vascular procedures, such as intravenous embolization of portosystemic shunts. Functional division of the canine liver similar to human models is possible. The left lateral and right medial lobes can be consistently divided into surgically resectable functional areas and partial lobectomies can be performed following a functional model; further study in clinically affected animals would be required to investigate the relevance of this functional model in the dog. © Copyright 2014 by The American College of Veterinary Surgeons.

  4. Manipulation of food intake and weight dynamics using retrograde neural gastric electrical stimulation in a chronic canine model

    NARCIS (Netherlands)

    Aelen, P.; Neshev, E.; Cholette, M.; Crisanti, K.; Mitchell, P.; De bru, E.; Church, N.; Mintchev, M.P.

    2008-01-01

    Neural gastric electrical stimulation (NGES) could be a new technique for treating obesity. However, chronic animal experimentation exploring the efficacy of this therapy is lacking. In this study we investigated the utility of retrograde NGES in a chronic canine model. Nine mongrel dogs (26.8 ± 5.2

  5. The canine bilateral groove model of osteoarthritis

    NARCIS (Netherlands)

    Intema, F.; Groot, J. de; Elshof, B.; Vianen, M.E.; Yocum, S.; Zuurmond, A.; Mastbergen, S.C.; Lafeber, F.P.

    2008-01-01

    In studies aimed at local treatment of experimental osteoarthritis (OA) it is optimal to have an internal (untreated) OA control. Such an approach excludes interanimal variation, and allows paired statistical evaluation of treatment efficacy. For this purpose, we developed and characterized a

  6. A canine distemper model of virus-induced anergy.

    Science.gov (United States)

    Mangi, R J; Munyer, T P; Krakowka, S; Jacoby, R O; Kantor, F S

    1976-05-01

    For development of an animal model of virus-induced anergy, the effect of canine distemper virus (CDV) upon cell-mediated immunity in dogs was investigated. First, canine cutaneous reactions and in vitro lymphocyte responses to soluble protein antigens were characterized. Dogs immunized with picryl guinea pig albumin and with keyhole limpet hemocyanin (both in complete Freund's adjuvant) responded reproducibly to intracutaneous challenge with these antigens. Reactivity peaked in 20-40 days (maximal induration, 6-50 mm). Lymphocytes from these animals responded in vitro to stimulation with keyhole limpet hemocyanin or purified protein derivative. This stimulation was antigen-specific and was maximal on day 6 of culture. Infection with CDV depressed cutaneous reactivity and lymphocyte response in vitro to antigens and mitogens. This effect was transient in animals previously vaccinated with attenuated CDV; however, gnotobiotic puppies (susceptible to CDV) had prolonged depression of cell-mediated immunity and lymphopenia. Some of these animals developed neurologic symptoms and died. The findings indicate that CDV infection is a potentially useful model for study of virus-induced depression of T (thymus)-cell responses and support the hypothesis that there is more than one mechanism responsible for this phenomenon.

  7. Constructing canine carotid artery stenosis model by endovascular technique

    International Nuclear Information System (INIS)

    Cheng Guangsen; Liu Yizhi

    2005-01-01

    Objective: To establish a carotid artery stenosis model by endovascular technique suitable for neuro-interventional therapy. Methods: Twelve dogs were anesthetized, the unilateral segments of the carotid arteries' tunica media and intima were damaged by a corneous guiding wire of home made. Twenty-four carotid artery stenosis models were thus created. DSA examination was performed on postprocedural weeks 2, 4, 8, 10 to estimate the changes of those stenotic carotid arteries. Results: Twenty-four carotid artery stenosis models were successfully created in twelve dogs. Conclusions: Canine carotid artery stenosis models can be created with the endovascular method having variation of pathologic characters and hemodynamic changes similar to human being. It is useful for further research involving the new technique and new material for interventional treatment. (authors)

  8. Pathogenesis of canine distemper virus in experimentally infected raccoon dogs, foxes, and minks.

    Science.gov (United States)

    Zhao, Jianjun; Shi, Ning; Sun, Yangang; Martella, Vito; Nikolin, Veljko; Zhu, Chunsheng; Zhang, Hailing; Hu, Bo; Bai, Xue; Yan, Xijun

    2015-10-01

    Canine distemper virus (CDV) infects a broad range of carnivores and causes a highly contagious disease with severe immunosuppression. The disease severity markedly varies in different species. To investigate the pathogenesis of CDV in raccoon dog (Nyctereutes procyonoides), fox (Vulpes vulpes) and mink (Neovison vison) species, three groups of CDV sero-negative animals were infected with CDV strain LN(10)1. This CDV strain belongs to the Asia-1 genotype, which is epidemiologically predominant in carnivores in China. CDV infection provoked marked differences in virulence in the three species that were studied. Raccoon dogs developed fever, severe conjunctivitis, and pathological lesions, with 100% (5/5) mortality and with high viral RNA loads in organs within 15 days post infection (dpi). In infected foxes, the onset of the disease was delayed, with 40% (2/5) mortality by 21 dpi. Infected minks developed only mild clinical signs and pathological lesions, and mortality was not observed. Raccoon dogs and foxes showed more severe immune suppression (lymphopenia, decreased lymphocyte proliferation, viremia and low-level virus neutralizing antibodies) than minks. We also observed a distinct pattern of cytokine mRNA transcripts at different times after infection. Decreased IFN-γ and IL-4 mRNA responses were evident in the animals with fatal disease, while up-regulation of these cytokines was observed in the animals surviving the infection. Increased TNF-α response was detected in animals with mild or severe clinical signs. Based on the results, we could distinguish three different patterns of disease after experimental CDV infection, e.g. a mild form in minks, a moderate form in foxes and a severe disease in raccoon dogs. The observed differences in susceptibility to CDV could be related to distinct host cytokine profiles. Comparative evaluation of CDV pathogenesis in various animal species is pivotal to generate models suitable for the evaluation of CDV

  9. Endovascular treatment of wide-necked aneurysms using stents combined with electrolytic detachable coils in a canine model

    International Nuclear Information System (INIS)

    Liu Jianmin; Zhang Xin; Zhou Xiaoping; Hong Bo; Xu Yi; Huang Qinghai; Zhang Long; She Jiagui; Zhao Rui

    2004-01-01

    Objective: To assess hemodynamics and histology of the aneurysms by treating experimental wide-necked aneurysms endovascularly with a combination of stents and electrolytic detachable coils. Methods: An experimental model was surgically constructed in the necks of six canines for simulating intracranial wide-necked aneurysms. Balloon-expandable metal stents were positioned across the aneurysms in bilateral carotid arteries of six canines with additional intraaneurysmal placement of detachable microcoils in only unilateral carotid artery of each canine. Sonography and angiography were performed in different stages and histologic examinations were achieved finally. Results: Stent placement was successful in all six canines. Aneurysms treated with only stents placement showed no significant thrombus formation with slow growing of neointima over the neck of the aneurysm. Thrombosis occurred in the aneurysms treated with stents and coils in a short time and neointima covered the neck of the aneurysms completely. Conclusions: Endovascular treatment of wide-necked aneurysms using stents combined with electrolytic detachable coils may prevent re-rupture of the aneurysms and promote neointima formation over the neck of the aneurysms. (authors)

  10. Glycogen storage disease type Ia in canines: a model for human metabolic and genetic liver disease.

    Science.gov (United States)

    Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B; Lee, Young Mok; Chou, Janice Y; Byrne, Barry J; Correia, Catherine E; Mah, Cathryn S; Weinstein, David A; Conlon, Thomas J

    2011-01-01

    A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including "lactic acidosis", larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  11. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

    Directory of Open Access Journals (Sweden)

    Andrew Specht

    2011-01-01

    Full Text Available A canine model of Glycogen storage disease type Ia (GSDIa is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  12. Bone compaction enhances implant fixation in a canine gap model

    DEFF Research Database (Denmark)

    Kold, Søren; Rahbek, Ole; Toft, Marianne

    2005-01-01

    A new bone preparation technique, compaction, has increased fixation of implants inserted with exact-fit or press-fit to bone. Furthermore, a demonstrated spring-back effect of compacted bone might be of potential value in reducing the initial gaps that often exist between clinical inserted...... implants and bone. However, it is unknown whether the compression and breakage of trabeculae during the compaction procedure results in impaired gap-healing of compacted bone. Therefore, we compared compaction with conventional drilling in a canine gap model. Grit-blasted titanium implants (diameter 6 mm...... that the beneficial effect of reduced gap size, as compacted bone springs back, is not eliminated by an impaired gap-healing of compacted bone....

  13. Canine as a biomedical research model: immunological, hematological, and oncological aspects

    International Nuclear Information System (INIS)

    Shifrine, M.; Wilson, F.D.

    1980-01-01

    The canine has been used as a biomedical research model in radiation studies by a number of laboratories supported primarily by the US Department of Energy and its predecessors. These studies were unique in that they covered the life spans of the canines and permitted the collection of data from birth to death under controlled conditions. Since these were multiparametric studies, an extensive data base has been established, not the least of which are normative values covering all biologic systems, including immunohematology. The canine model has also been extensively used by other groups, such as transplantation biologists. The virtues of the canine as a model in these and many other endeavors are becoming increasingly more apparent with the passing of time. One of the primary goals of this volume was to compile the knowledge and experience of researchers using the canine model and to focus their expertise on furthering the use of the canine for studies in immunology, hematology, and oncology. We have attempted to present some of the contemporary, diverse uses of the canine in biomedical research, emphasizing immunologic endpoints, and also to present in detail some of the latest technology used in such studies

  14. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

    OpenAIRE

    Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B.; Lee, Young Mok; Chou, Janice Y.; Byrne, Barry J.; Correia, Catherine E.; Mah, Cathryn S.; Weinstein, David A.; Conlon, Thomas J.

    2011-01-01

    A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size,...

  15. Comparative strain analysis of Anaplasma phagocytophilum infection and clinical outcomes in a canine model of granulocytic anaplasmosis.

    Science.gov (United States)

    Scorpio, Diana G; Dumler, J Stephen; Barat, Nicole C; Cook, Judith A; Barat, Christopher E; Stillman, Brett A; DeBisceglie, Kristen C; Beall, Melissa J; Chandrashekar, Ramaswamy

    2011-03-01

    A pilot study was conducted to determine whether existing human or canine strains of Anaplasma phagocytophilum would reproduce clinical disease in experimentally inoculated dogs similar to dogs with naturally acquired granulocytic anaplasmosis. Six hounds were inoculated intravenously with one human and two canine strains of A. phagocytophilum that were propagated in vitro in HL-60 cells or in infected autologous neutrophils. Infected dogs were monitored for lethargy, anorexia, petechiae, lymphadenopathy, and fever. Dogs were assessed for complete blood count (CBC), serum chemistry, and serology (IFA and SNAP® 4Dx®); for A. phagocytophilum blood load by quantitative polymerase chain reaction; and for cytokine production. Prominent clinical signs were generalized lymphadenopathy and scleral injection; only one dog developed fever lasting 4 days. Notable laboratory alterations included sustained leukopenia and thrombocytopenia in all dogs. A. phagocytophilum morulae were noted in blood between days 10 and 11, although all dogs retained A. phagocytophilum DNA in blood through day 60. All dogs seroconverted by days 10-15 by IFA, and by days 17-30 by SNAP 4Dx; cytokine analyses revealed 10-fold increases in interleukin-2 and interleukin-18 in the neutrophil-propagated 98E4 strain-infected dog. All A. phagocytophilum strains produced infection, although canine 98E4 strain reproduced clinical signs, hematologic changes, and inflammatory cytokine elevations most consistent with granulocytic anaplasmosis when recognized clinically. Therefore, this strain should be considered for use in future studies of A. phagocytophilum canine infection models.

  16. Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

    International Nuclear Information System (INIS)

    Kodama, Atsushi; Yanai, Tokuma; Sakai, Hiroki; Matsuura, Satoko; Murakami, Mami; Murai, Atsuko; Mori, Takashi; Maruo, Kouji; Kimura, Tohru; Masegi, Toshiaki

    2009-01-01

    Human hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes. Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factors (bFGF), flt-1 and flk-1 (receptors of VEGF-A), FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR), using canine-specific primer sets. Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF) was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the other tumors. We established 6 xenograft canine HSA

  17. Canine degenerative myelopathy: a model of human amyotrophic lateral sclerosis.

    Science.gov (United States)

    Nardone, Raffaele; Höller, Yvonne; Taylor, Alexandra C; Lochner, Piergiorgio; Tezzon, Frediano; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2016-02-01

    Canine degenerative myelopathy (CDM) represents a unique naturally occurring animal model for human amyotrophic lateral sclerosis (ALS) because of similar clinical signs, neuropathologic findings, and involvement of the superoxide dismutase 1 (SOD1) mutation. A definitive diagnosis can only be made postmortem through microscopic detection of axonal degeneration, demyelination and astroglial proliferation, which is more severe in the dorsal columns of the thoracic spinal cord and in the dorsal portion of the lateral funiculus. Interestingly, the muscle acetylcholine receptor complexes are intact in CDM prior to functional impairment, thus suggesting that muscle atrophy in CDM does not result from physical denervation. Moreover, since sensory involvement seems to play an important role in CDM progression, a more careful investigation of the sensory pathology in ALS is also warranted. The importance of SOD1 expression remains unclear, while oxidative stress and denatured ubiquinated proteins appear to play a crucial role in the pathogenesis of CDM. In this updated narrative review we performed a systematic search of the published studies on CDM that may shed light on the pathophysiological mechanisms of human ALS. A better understanding of the factors that determine the disease progression in CDM may be beneficial for the development of effective treatments for ALS. Copyright © 2015 Elsevier GmbH. All rights reserved.

  18. Intra- and interspecies gene expression models for predicting drug response in canine osteosarcoma.

    Science.gov (United States)

    Fowles, Jared S; Brown, Kristen C; Hess, Ann M; Duval, Dawn L; Gustafson, Daniel L

    2016-02-19

    Genomics-based predictors of drug response have the potential to improve outcomes associated with cancer therapy. Osteosarcoma (OS), the most common primary bone cancer in dogs, is commonly treated with adjuvant doxorubicin or carboplatin following amputation of the affected limb. We evaluated the use of gene-expression based models built in an intra- or interspecies manner to predict chemosensitivity and treatment outcome in canine OS. Models were built and evaluated using microarray gene expression and drug sensitivity data from human and canine cancer cell lines, and canine OS tumor datasets. The "COXEN" method was utilized to filter gene signatures between human and dog datasets based on strong co-expression patterns. Models were built using linear discriminant analysis via the misclassification penalized posterior algorithm. The best doxorubicin model involved genes identified in human lines that were co-expressed and trained on canine OS tumor data, which accurately predicted clinical outcome in 73 % of dogs (p = 0.0262, binomial). The best carboplatin model utilized canine lines for gene identification and model training, with canine OS tumor data for co-expression. Dogs whose treatment matched our predictions had significantly better clinical outcomes than those that didn't (p = 0.0006, Log Rank), and this predictor significantly associated with longer disease free intervals in a Cox multivariate analysis (hazard ratio = 0.3102, p = 0.0124). Our data show that intra- and interspecies gene expression models can successfully predict response in canine OS, which may improve outcome in dogs and serve as pre-clinical validation for similar methods in human cancer research.

  19. Effects of Recombinant Human Bone Morphogenetic Protein-2 on Vertical Bone Augmentation in a Canine Model.

    Science.gov (United States)

    Hsu, Yung-Ting; Al-Hezaimi, Khalid; Galindo-Moreno, Pablo; O'Valle, Francisco; Al-Rasheed, Abdulaziz; Wang, Hom-Lay

    2017-09-01

    Vertical bone augmentation (VBA) remains unpredictable and challenging for most clinicians. This study aims to compare hard tissue outcomes of VBA, with and without recombinant human bone morphogenetic protein (rhBMP)-2, under space-making titanium mesh in a canine model. Eleven male beagle dogs were used in the study. Experimental ridge defects were created to form atrophic ridges. VBA was performed via guided bone regeneration using titanium mesh and allografts. In experimental hemimandibles, rhBMP-2/absorbable collagen sponge was well mixed with allografts prior to procedures, whereas a control buffer was applied within controls. Dogs were euthanized after a 4-month healing period. Clinical and radiographic examinations were performed to assess ridge dimensional changes. In addition, specimens were used for microcomputed tomography (micro-CT) assessment and histologic analysis. Membrane exposure was found on five of 11 (45.5%) rhBMP-2-treated sites, whereas it was found on nine of 11 (81.8%) non-rhBMP-2-treated sites. Within 4 months of healing, rhBMP-2-treated sites showed better radiographic bone density, greater defect fill, and significantly more bone gain in ridge height (P 0.05). Under light microscope, predominant lamellar patterns were found in the specimen obtained from rhBMP-2 sites. With inherent limitations of the canine model and the concern of such a demanding surgical technique, current findings suggest that the presence of rhBMP-2 in a composite graft allows an increase of vertical gain, with formation of ectopic bone over the titanium mesh in comparison with non-rhBMP-2 sites.

  20. Saphenous Venous Ablation with Hot Contrast in a Canine Model

    International Nuclear Information System (INIS)

    Prasad, Amit; Qian Zhong; Kirsch, David; Eissa, Marna; Narra, Pavan; Lopera, Jorge; Espinoza, Carmen G.; Castaneda, Wifrido

    2008-01-01

    Purpose. To determine the feasibility, efficacy, and safety of thermal ablation of the saphenous vein with hot contrast medium. Methods. Twelve saphenous veins of 6 dogs were percutaneously ablated with hot contrast medium. In all animals, ablation was performed in the vein of one leg, followed by ablation in the contralateral side 1 month later. An occlusion balloon catheter was placed in the infragenicular segment of the saphenous vein via a jugular access to prevent unwanted thermal effects on the non-target segment of the saphenous vein. After inflation of the balloon, 10 ml of hot contrast medium was injected under fluoroscopic control through a sheath placed in the saphenous vein above the ankle. A second 10 ml injection of hot contrast medium was made after 5 min in each vessel. Venographic follow-up of the ablated veins was performed at 1 month (n = 12) and 2 months (n = 6). Results. Follow-up venograms showed that all ablated venous segments were occluded at 1 month. In 6 veins which were followed up to 2 months, 4 (66%) remained occluded, 1 (16%) was partially patent, and the remaining vein (16%) was completely patent. In these latter 2 cases, an inadequate amount of hot contrast was delivered to the lumen due to a closed balloon catheter downstream which did not allow contrast to displace blood within the vessel. Discussion. Hot contrast medium thermal ablation of the saphenous vein appears feasible, safe, and effective in the canine model, provided an adequate amount of embolization agent is used

  1. A cell kinetic model of granulopoiesis under radiation exposure: Extension from rodents to canines and humans

    International Nuclear Information System (INIS)

    Hu, S.; Cucinotta, F. A.

    2011-01-01

    As significant ionising radiation exposure will occur during prolonged space travel in future, it is essential to understand their adverse effects on the radiosensitive organ systems that are important for immediate survival of humans, e.g. the haematopoietic system. In this paper, a bio-mathematical model of granulopoiesis is used to analyse the granulocyte changes seen in the blood of mammalians under acute and continuous radiation exposure. This is one of a set of haematopoietic models that have been successfully utilised to simulate and interpret the experimental data of acute and chronic radiation on rodents. Extension to canine and human systems indicates that the results of the model are consistent with the cumulative experimental and empirical data from various sources, implying the potential to integrate them into one united model system to monitor the haematopoietic response of various species under irradiation. The suppression of granulocytes' level of a space traveller under chronic stress of low-dose irradiation as well as the granulopoietic response when encountering a historically large solar particle event is also discussed. (authors)

  2. Does Loading Influence the Severity of Cartilage Degeneration in the Canine Groove-Model of OA?

    NARCIS (Netherlands)

    Vos, Petra; Intema, Femke; van El, Benno; DeGroot, Jeroen; Bijlsma, J. W. J.; Lafeber, Floris; Mastbergen, Simon

    2009-01-01

    Many animal models are used to study osteoarthritis (OA). In these models the role of joint loading in the development of CA is not fully understood. We studied the effect of loading on the development of CIA in the canine Groove-model. In ten female beagle dogs OA was induced in one knee according

  3. Experimental determination of net protein charge and A(tot) and K(a) of nonvolatile buffers in canine plasma.

    Science.gov (United States)

    Constable, Peter D; Stämpfli, Henry R

    2005-01-01

    Acid-base abnormalities frequently are present in sick dogs. The mechanism for an acid-base disturbance can be determined with the simplified strong ion approach, which requires accurate values for the total concentration of plasma nonvolatile buffers (A(tot)) and the effective dissociation constant for plasma weak acids (K(a)). The aims of this study were to experimentally determine A(tot) and K(a) values for canine plasma. Plasma was harvested from 10 healthy dogs; the concentrations of quantitatively important strong ions (Na+, K+, Ca2+, Mg2+, Cl-, L-lactate) and nonvolatile buffer ions (total protein, albumin, phosphate) were determined; and the plasma was tonometered with CO2 at 37 degrees C. Strong ion difference (SID) was calculated from the measured strong ion concentrations, and nonlinear regression was used to estimate values for A(tot) and K(a), which were validated with data from an in vitro and in vivo study. Mean (+/- SD) values for canine plasma were A(tot) = (17.4 +/- 8.6) mM (equivalent to 0.273 mmol/g of total protein or 0.469 mmol/g of albumin); K(a) = (0.17 +/- 0.11) x 10(-7); pK(a) = 7.77. The calculated SID for normal canine plasma (pH = 7.40; P(CO2) = 37 mm Hg; [total protein] = 64 g/L) was 27 mEq/L. The net protein charge for normal canine plasma was 0.25 mEq/g of total protein or 0.42 mEq/g of albumin. Application of the experimentally determined values for A(tot), K(a), and net protein charge should improve understanding of the mechanism for complex acid-base disturbances in dogs.

  4. Effects of aurothiomalate treatment on canine osteosarcoma in a murine xenograft model.

    Science.gov (United States)

    Scharf, Valery F; Farese, James P; Siemann, Dietmar W; Abbott, Jeffrey R; Kiupel, Matti; Salute, Marc E; Milner, Rowan J

    2014-03-01

    Osteosarcoma is a highly fatal cancer, with most patients ultimately succumbing to metastatic disease. The purpose of this study was to evaluate the effects of the antirheumatoid drug aurothiomalate on canine and human osteosarcoma cells and on canine osteosarcoma growth and metastasis in a mouse xenograft model. We hypothesized that aurothiomalate would decrease osteosarcoma cell survival, tumor cellular proliferation, tumor growth, and metastasis. After performing clonogenic assays, aurothiomalate or a placebo was administered to 54 mice inoculated with canine osteosarcoma. Survival, tumor growth, embolization, metastasis, histopathology, cell proliferation marker Ki67, and apoptosis marker caspase-3 were compared between groups. Statistical analysis was carried out using the Kaplan-Meier method with the log-rank test and one-way analysis of variance with the Tukey's test or Dunn's method. Aurothiomalate caused dose-dependent inhibition of osteosarcoma cell survival (Posteosarcoma cell survival and reduced tumor cell proliferation, growth, embolization, and pulmonary metastasis. Given aurothiomalate's established utility in canine and human medicine, our results suggest that this compound may hold promise as an adjunctive therapy for osteosarcoma. Further translational research is warranted to better characterize the dose response of canine and human osteosarcoma to aurothiomalate.

  5. Vascularized bone grafting in a canine carpal avascular necrosis model

    NARCIS (Netherlands)

    Willems, Wouter F.; Alberton, Gregory M.; Bishop, Allen T.; Kremer, Thomas

    2011-01-01

    Limited experimental research has been performed on the treatment of avascular necrosis (AVN) by vascularized bone grafting. A new model simulating carpal AVN was created to investigate surgical revascularization of necrotic bone. In seven mongrel dogs, AVN was induced by removal of the radial

  6. Hypercapnic Acidosis Preserves Gastric Mucosal Microvascular Oxygen Saturation in a Canine Model of Hemorrhage.

    NARCIS (Netherlands)

    Schwartges, Ingo; Picker, Olaf; Beck, Christopher; Scheeren, Thomas W. L.; Schwarte, Lothar A.

    2010-01-01

    The authors aimed to clarify the effects of hypercapnic acidosis and its timing on gastric mucosal oxygenation in a canine model of hemorrhage. This was designed as a prospective, controlled, randomized animal study set in a university research laboratory. Five chronically instrumented dogs were

  7. Combined stent implantation and embolization with liquid 2-polyhydroxyethyl methacrylate for treatment of experimental canine wide-necked aneurysms

    Energy Technology Data Exchange (ETDEWEB)

    Klisch, J.; Zitt, J.; Schumacher, M. [Section of Neuroradiology, University of Freiburg (Germany); Schellhammer, F. [Department of Radiology, University of Cologne, Cologne (Germany); Scheufler, K.M. [Department of Neurosurgery, University of Freiburg (Germany); Pagenstecher, A. [Department of Neuropathology, University of Freiburg, Freiburg (Germany); Nagursky, H. [Department of Oral and Maxillofacial Surgery, University of Freiburg, Freiburg (Germany)

    2002-06-01

    The purpose of the study was the evaluation of 2-polyhydroxyethyl methacrylate (2-P-HEMA) for endovascular liquid embolization of experimental side-wall aneurysms following stent protection in a canine model. The swelling behaviour and polymerization characteristics of 2-P-HEMA in different solutions were investigated in vitro. Different methods for applications were tested in a latex aneurysm model under pulsatile flow conditions. Twenty broad-based carotid side-wall aneurysms were microsurgically produced in five dogs. Four weeks after surgery self-expandable nitinol stents were placed, covering the orifice of the aneurysms. 2-P-HEMA was injected via a microcatheter, which was positioned through the meshwork of the stent. Control angiography was performed immediately after treatment and after 1, 6 and 9 months. In-vivo stent placement succeeded in all but one case. Two aneurysms occluded spontaneously after stent placement. Combined embolization of 17 aneurysms using a stent and 2-P-HEMA was performed. Eleven aneurysms could be primarily completely occluded (65%). A small remaining neck was evident in six aneurysms. Efflux of 2-P-HEMA during the process of embolization was observed in seven aneurysms, due to an excess volume of 2-P-HEMA. The excessive 2-P-HEMA led to significant vessel stenosis in two cases. Two carotid arteries (three treated aneurysms) occluded after 1 month, due to insufficient anticoagulation management. Histological examination of embolized aneurysms revealed no foreign-body or inflammatory reaction. A smooth neo-intimal layer covered the stented vessel segment. Liquid embolization of side-wall aneurysms with 2-P-HEMA is technically feasible. Embolotherapy of aneurysms with liquid agents still has the risk that embolic material will exit even when it is stent-protected. To avoid this problem, stents with smaller strut diameter and/or additional balloon-protection are required. The inert 2-P-HEMA seems to be a promising agent for combining

  8. A novel method for objective vision testing in canine models of inherited retinal disease.

    Science.gov (United States)

    Gearhart, Patricia M; Gearhart, Chris C; Petersen-Jones, Simon M

    2008-08-01

    The use of canine models of retinal disease in the development of therapeutic strategies for inherited retinal disorders is a growing area of research. To evaluate accurately the success of potential vision-enhancing treatments, reliable methods for objectively assessing visual function in canine models is necessary. A simple vision-testing device was constructed that consisted of a junction box with four exit tunnels. Dogs were placed in the junction box and given one vision-based choice for exit. The first-choice tunnel and time to exit were recorded and analyzed. Two canine models of retinal disease with distinct molecular defects, a null mutation in the gene encoding the alpha subunit of rod cyclic GMP phosphodiesterase (PDE6A), and a null mutation in the gene encoding a retinal pigment epithelium-specific protein (RPE65) were tested and compared to those in unaffected dogs. With the use of bright light versus dim red light, the test differentiated between unaffected dogs and dogs affected with either mutation with a high degree of certainty. The white-light intensity series showed a significantly different performance between the unaffected and affected dogs. A significant difference in performance was detected between the dogs with each mutation. The results indicate that this novel canine vision-testing method is an accurate and sensitive means of distinguishing between unaffected dogs and dogs affected with two different forms of inherited retinal disease and should be useful as a means of assessing response to therapy in future studies.

  9. The importance of regional models in assessing canine cancer incidences in Switzerland.

    Science.gov (United States)

    Boo, Gianluca; Leyk, Stefan; Brunsdon, Christopher; Graf, Ramona; Pospischil, Andreas; Fabrikant, Sara Irina

    2018-01-01

    Fitting canine cancer incidences through a conventional regression model assumes constant statistical relationships across the study area in estimating the model coefficients. However, it is often more realistic to consider that these relationships may vary over space. Such a condition, known as spatial non-stationarity, implies that the model coefficients need to be estimated locally. In these kinds of local models, the geographic scale, or spatial extent, employed for coefficient estimation may also have a pervasive influence. This is because important variations in the local model coefficients across geographic scales may impact the understanding of local relationships. In this study, we fitted canine cancer incidences across Swiss municipal units through multiple regional models. We computed diagnostic summaries across the different regional models, and contrasted them with the diagnostics of the conventional regression model, using value-by-alpha maps and scalograms. The results of this comparative assessment enabled us to identify variations in the goodness-of-fit and coefficient estimates. We detected spatially non-stationary relationships, in particular, for the variables related to biological risk factors. These variations in the model coefficients were more important at small geographic scales, making a case for the need to model canine cancer incidences locally in contrast to more conventional global approaches. However, we contend that prior to undertaking local modeling efforts, a deeper understanding of the effects of geographic scale is needed to better characterize and identify local model relationships.

  10. Vaccines for canine leishmaniasis

    Directory of Open Access Journals (Sweden)

    Clarisa B. Palatnik-De-Sousa

    2012-04-01

    Full Text Available Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global-warming, co-infection with immunosuppressive diseases and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL in the Americas, the Middle East, Central Asia, China and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine visceral leishmaniasis. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans

  11. Lateral Cricoarytenoid Release: Development of a Novel Surgical Treatment Option for Adductor Spasmodic Dysphonia in a Canine Laryngeal Model.

    Science.gov (United States)

    Park, Andrea M; Paniello, Randal C

    2016-09-01

    To investigate the efficacy of a novel adductor muscle-releasing technique designed to decrease the force of vocal fold adduction, as a potential surgical therapy for patients with adductor spasmodic dysphonia (ADSD). Experimental animal study. A canine laryngeal model was used to assess the acute and sustained efficacy of a lateral cricoarytenoid (LCA) muscle release. A total of 34 canine hemilaryngeal preparations were divided among 7 experimental groups. The LCA muscle was separated from its cricoid cartilage origin via an open, anterior, submucosal approach. The laryngeal adductory pressures (LAP) were assessed pre- and post-muscle release via direct recurrent laryngeal nerve stimulation. Measurements were repeated at 1.5, 3, or 6 months postoperatively. Another study evaluated release of the thyroarytenoid (TA) muscle from its thyroid cartilage origin. Releasing the LCA muscle demonstrated a significant decrease in LAP acutely and was maintained at all 3 time points with the aid of a barrier (P < .05). Without the barrier, the LCA muscle reattached to the cricoid. Acute release of the TA muscle did not significantly decrease the LAP. The proposed LCA release procedure may provide patients with a permanent treatment option for ADSD. However, longer-term studies and human trials are needed. © The Author(s) 2016.

  12. Flow cytometric techniques for detection of candidate cancer stem cell subpopulations in canine tumour models.

    Science.gov (United States)

    Blacking, T M; Waterfall, M; Samuel, K; Argyle, D J

    2012-12-01

    The cancer stem cell (CSC) hypothesis proposes that tumour growth is maintained by a distinct subpopulation of 'CSC'. This study applied flow cytometric methods, reported to detect CSC in both primary and cultured cancer cells of other species, to identify candidate canine subpopulations. Cell lines representing diverse canine malignancies, and cells derived from spontaneous canine tumours, were evaluated for expression of stem cell-associated surface markers (CD34, CD44, CD117 and CD133) and functional properties [Hoecsht 33342 efflux, aldehyde dehydrogenase (ALDH) activity]. No discrete marker-defined subsets were identified within established cell lines; cells derived directly from spontaneous tumours demonstrated more heterogeneity, although this diminished upon in vitro culture. Functional assays produced variable results, suggesting context-dependency. Flow cytometric methods may be adopted to identify putative canine CSC. Whilst cell lines are valuable in assay development, primary cells may provide a more rewarding model for studying tumour heterogeneity in the context of CSC. However, it will be essential to fully characterize any candidate subpopulations to ensure that they meet CSC criteria. © 2011 Blackwell Publishing Ltd.

  13. Development of an Arthroscopic Joint Capsule Injury Model in the Canine Shoulder.

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    David Kovacevic

    Full Text Available The natural history of rotator cuff tears can be unfavorable as patients develop fatty infiltration and muscle atrophy that is often associated with a loss of muscle strength and shoulder function. To facilitate study of possible biologic mechanisms involved in early degenerative changes to rotator cuff muscle and tendon tissues, the objective of this study was to develop a joint capsule injury model in the canine shoulder using arthroscopy.Arthroscopic surgical methods for performing a posterior joint capsulectomy in the canine shoulder were first defined in cadavers. Subsequently, one canine subject underwent bilateral shoulder joint capsulectomy using arthroscopy, arthroscopic surveillance at 2, 4 and 8 weeks, and gross and histologic examination of the joint at 10 weeks.The canine subject was weight-bearing within eight hours after index and follow-up surgeries and had no significant soft tissue swelling of the shoulder girdle or gross lameness. Chronic synovitis and macroscopic and microscopic evidence of pathologic changes to the rotator cuff bony insertions, tendons, myotendinous junctions and muscles were observed.This study demonstrates feasibility and proof-of-concept for a joint capsule injury model in the canine shoulder. Future work is needed to define the observed pathologic changes and their role in the progression of rotator cuff disease. Ultimately, better understanding of the biologic mechanisms of early progression of rotator cuff disease may lead to clinical interventions to halt or slow this process and avoid the more advanced and often irreversible conditions of large tendon tears with muscle fatty atrophy.

  14. The establishment of transmissible venereal tumor lung cancer model in canine and the observation of its biological characteristics

    International Nuclear Information System (INIS)

    Sun Zhichao; Dong Weihua; Xiao Xiangsheng; Zhu Ruimin; Chen mofan; Wang Zhi

    2010-01-01

    Objective: To establish an allogeneic transplanted lung cancer model in canine by percutaneously injecting canine transmissible venereal tumor (CTVT) cell suspension and to observe its biological characteristics. Methods: Under CT guidance fresh CTVT cell suspension was inoculated into the middle or posterior lobe of lungs through percutaneous puncturing needle in 12 beagle dogs. Cyclosporin was administrated orally to obtain immunosuppression. Tumor growth and metastasis were judged by chest CT scanning at regular intervals (every 1-2 weeks). The daily mental and physical condition of the dogs was observed. Autopsy and pathological examination were performed when the animals died naturally or at the tenth week after the procedure when the animals were sacrificed. Results: A total of 15 sites were inoculated in 12 dogs. The formation of tumor was observed in 2 dogs at the fifth week and in 9 dogs at the sixth week. Ten weeks after the inoculation the formation of tumor was detected in 10 inoculated points in 9 dogs, the inoculation success rate was 66.67%. The mean largest diameter of the tumor at 6, 8 and 10 weeks after the inoculation was (1.059 ± 0.113)cm, (1.827 ± 0.084)cm and (2.189 ± 0.153)cm, respectively. The largest diameter of the tumor nodule was 3.5 cm. Moderate to severe pleural effusion and mediastinal lymph nodes metastasis were found in all the dogs that showed the formation of the tumor. Conclusion: Percutaneous CTVT cell suspension injection can establish an allogeneic canine lung cancer model, which is helpful for the experimental studies related to lung cancer. (authors)

  15. A computerized MRI biomarker quantification scheme for a canine model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Wang, Jiahui; Fan, Zheng; Vandenborne, Krista; Walter, Glenn; Shiloh-Malawsky, Yael; An, Hongyu; Kornegay, Joe N; Styner, Martin A

    2013-09-01

    Golden retriever muscular dystrophy (GRMD) is a widely used canine model of Duchenne muscular dystrophy (DMD). Recent studies have shown that magnetic resonance imaging (MRI) can be used to non-invasively detect consistent changes in both DMD and GRMD. In this paper, we propose a semiautomated system to quantify MRI biomarkers of GRMD. Our system was applied to a database of 45 MRI scans from 8 normal and 10 GRMD dogs in a longitudinal natural history study. We first segmented six proximal pelvic limb muscles using a semiautomated full muscle segmentation method. We then performed preprocessing, including intensity inhomogeneity correction, spatial registration of different image sequences, intensity calibration of T2-weighted and T2-weighted fat-suppressed images, and calculation of MRI biomarker maps. Finally, for each of the segmented muscles, we automatically measured MRI biomarkers of muscle volume, intensity statistics over MRI biomarker maps, and statistical image texture features. The muscle volume and the mean intensities in T2 value, fat, and water maps showed group differences between normal and GRMD dogs. For the statistical texture biomarkers, both the histogram and run-length matrix features showed obvious group differences between normal and GRMD dogs. The full muscle segmentation showed significantly less error and variability in the proposed biomarkers when compared to the standard, limited muscle range segmentation. The experimental results demonstrated that this quantification tool could reliably quantify MRI biomarkers in GRMD dogs, suggesting that it would also be useful for quantifying disease progression and measuring therapeutic effect in DMD patients.

  16. Antifibrillatory effects of renal denervation on ventricular fibrillation in a canine model of pacing-induced heart failure.

    Science.gov (United States)

    Luo, Qingzhi; Jin, Qi; Zhang, Ning; Huang, Shangwei; Han, Yanxin; Lin, Changjian; Ling, Tianyou; Chen, Kang; Pan, Wenqi; Wu, Liqun

    2018-01-01

    .48 ± 0.2 versus 1.26 ± 0.11, P < 0.05) and decreased the dispersion of ARI by 25% (0.08 ± 0.02 versus 0.06 ± 0.01, P < 0.01) in the treated group compared with the HF group. The findings of this study suggest that RDN can attenuate ventricular electrical remodelling and exert a potential antifibrillatory action on VF in a canine model of pacing-induced HF. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

  17. Rapid maxillary anterior teeth retraction en masse by bone compression: a canine model.

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    Chufeng Liu

    Full Text Available The present study sought to establish an animal model to study the feasibility and safety of rapid retraction of maxillary anterior teeth en masse aided by alveolar surgery in order to reduce orthodontic treatment time.Extraction of the maxillary canine and alveolar surgery were performed on twelve adult beagle dogs. After that, the custom-made tooth-borne distraction devices were placed on beagles' teeth. Nine of the dogs were applied compression at 0.5 mm/d for 12 days continuously. The other three received no force as the control group. The animals were killed in 1, 14, and 28 days after the end of the application of compression.The tissue responses were assessed by craniometric measurement as well as histological examination. Gross alterations were evident in the experimental group, characterized by anterior teeth crossbite. The average total movements of incisors within 12 days were 4.63±0.10 mm and the average anchorage losses were 1.25±0.12 mm. Considerable root resorption extending into the dentine could be observed 1 and 14 days after the compression. But after consolidation of 28 days, there were regenerated cementum on the dentine. There was no apparent change in the control group. No obvious tooth loosening, gingival necrosis, pulp degeneration, or other adverse complications appeared in any of the dogs.This is the first experimental study for testing the technique of rapid anterior teeth retraction en masse aided by modified alveolar surgery. Despite a preliminary animal model study, the current findings pave the way for the potential clinical application that can accelerate orthodontic tooth movement without many adverse complications.It may become a novel method to shorten the clinical orthodontic treatment time in the future.

  18. Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids

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    Sathidpak Nantasanti

    2015-11-01

    Full Text Available The recent development of 3D-liver stem cell cultures (hepatic organoids opens up new avenues for gene and/or stem cell therapy to treat liver disease. To test safety and efficacy, a relevant large animal model is essential but not yet established. Because of its shared pathologies and disease pathways, the dog is considered the best model for human liver disease. Here we report the establishment of a long-term canine hepatic organoid culture allowing undifferentiated expansion of progenitor cells that can be differentiated toward functional hepatocytes. We show that cultures can be initiated from fresh and frozen liver tissues using Tru-Cut or fine-needle biopsies. The use of Wnt agonists proved important for canine organoid proliferation and inhibition of differentiation. Finally, we demonstrate that successful gene supplementation in hepatic organoids of COMMD1-deficient dogs restores function and can be an effective means to cure copper storage disease.

  19. Orthotopic model of canine osteosarcoma in athymic rats for evaluation of stereotactic radiotherapy.

    Science.gov (United States)

    Schwartz, Anthony L; Custis, James T; Harmon, Joseph F; Powers, Barbara E; Chubb, Laura S; LaRue, Susan M; Ehrhart, Nicole P; Ryan, Stewart D

    2013-03-01

    To develop an orthotopic model of canine osteosarcoma in athymic rats as a model for evaluating the effects of stereotactic radiotherapy (SRT) on osteosarcoma cells. 26 athymic nude rats. 3 experiments were performed. In the first 2 experiments, rats were injected with 1 × 10(6) Abrams canine osteosarcoma cells into the proximal aspect of the tibia (n = 12) or distal aspect of the femur (6). Tumor engraftment and progression were monitored weekly via radiography, luciferase imaging, and measurement of urine pyridinoline concentration for 5 weeks and histologic evaluation after euthanasia. In the third experiment, 8 rats underwent canine osteosarcoma cell injection into the distal aspect of the femur and SRT was administered to the affected area in three 12-Gy fractions delivered on consecutive days (total radiation dose, 36 Gy). Percentage tumor necrosis and urinary pyridinoline concentrations were used to assess local tumor control. The short-term effect of SRT on skin was also evaluated. Tumors developed in 10 of 12 tibial sites and all 14 femoral sites. Administration of SRT to rats with femoral osteosarcoma was feasible and successful. Mean tumor necrosis of 95% was achieved histologically, and minimal adverse skin effects were observed. The orthotopic model of canine osteosarcoma in rats developed in this study was suitable for evaluating the effects of local tumor control and can be used in future studies to evaluate optimization of SRT duration, dose, and fractionation schemes. The model could also allow evaluation of other treatments in combination with SRT, such as chemotherapy or bisphosphonate, radioprotectant, or parathyroid hormone treatment.

  20. Establishment and bronchial arteriography of the models of canine lung cancer

    International Nuclear Information System (INIS)

    Cao Xicai; Wang Xiaodong; Li Bin; Shi Jianguang; Liu Yong; Xu Nanxun; Ma Weijun; Yang Haixian; Bai Jingwen; Li Weidong; Liu Shuping; Liu Anpu

    2003-01-01

    Objective: To investigate the establishment and bronchial arteriography of the models of canine lung cancer, and to facilitate further diagnosis and treatment of lung cancer. Methods: Twenty-two dogs were respectively administrated with 3 ml suspension of lipiodol-ultrafluid mixed with 3- methylcholanthrene (MCA) and diethylnitrosamine (DEN). The suspension was injected into the diaphragmic lobe of right lung with the co-axial catheter through endotracheal intubation. The dogs were randomly divided into 5 groups, group A (4 dogs), B (4), C (4), D (5), and E (5), which were sacrificed after observation for 1, 3, 6, 12, and 18 months, respectively. Then the image analysis and histopathologic examinations were carried out at different period. 5 dogs in group E were examined by bronchial arteriography. Results: Peribronchiolitis and atelectasis appeared at early stage (one month). Chronic granulomatous inflammation and fibrosis of lung tissue were gradually formed after 3 months. Proliferation of stem cells in bronchioles and atypical hyperplasia were found from 6 to 12 months. At last, the squamous carcinoma and bronchioloalveolar carcinoma were induced after 18 months. The lung cancer and precancerous lesion were found in 4 of 5 dogs at the 18 th month. The bronchial arteriography in the 5 dogs showed that 3 bronchial arteries were found as the supplying blood artery to the tumor. Conclusion: The suspension of lipiodol-ultrafluid mixed with MCA and DEN was exactly injected with the co-axial catheter through endotracheal intubation to establish the models of canine lung cancer. The inducible rate of the method was high and the location of lung cancer was accurate. It was affirmed that the blood supply artery of canine lung cancer was bronchial artery. Bronchial arteriography was of momentous significance to the diagnosis of early lung cancer. The establishment of the models of canine lung cancer was significant in the diagnosis and treatment of lung cancer. The models

  1. Percutaneous intradiscal ozone (O3)-injection: an experimental study in canines

    International Nuclear Information System (INIS)

    Yu Zhijian; He Xiaofeng; Chen Yong; Zeng Qingle; Liu Chihong; Zhao Zhongqing; Lu Yong; Li Yanhao

    2002-01-01

    Objective: To evaluate the influence of ozone on normal nucleus pulpous and the safety of intradiscal ozone-injection for the treatment of herniated lumbar disc. Methods: Ozone was injected into selected lumbar discs (3 ml) and the para-spinal space (7 ml) with 20 G Chiba needle under fluoroscopy in five canines. The ozone concentration was 30 μg/ml and 50 μg/ml respectively. Two discs were selected for each concentration. Total 20 discs were injected. Three of the canines were given one-time ozone-injection and were sacrificed for pathology one week, one month and two months respectively after the procedure, and the other two canines were given two-time ozone-injection and were sacrificed one month and two months respectively after the procedure. The specimens including nucleus pulpous, end-plate, spinal cord, nerve root, and greater psoas muscle were observed macroscopically and microscopically. Results: No serious behavior abnormalities were observed in all animals. The atrophy of nucleus pulpous could be observed one month after ozone-injection due to significant reduction of water and extensive proliferation of collagenous fiber. The influence on the atrophy of nucleus pulpous demonstrated no apparent difference between the selected two concentrations of ozone, but was more apparent with two-time injection than that with one-time injection. The end-plates increased slightly or moderately in thickness in 16 simples and a few of fibers in greater psoas muscle suffered slight atrophy in 5 samples. Conclusion: It is suggested that percutaneous intradiscal ozone-injection is a safe method, and can cause gradual atrophy of nucleus pulpous. This study provides the evidence of the feasibility and value of this procedure's application in clinics

  2. The implantation of separating aortic stent-graft into the canine thoracic aorta: an experimental study

    International Nuclear Information System (INIS)

    Xia Jinguo; Shi Haibin; Yang Zhengqiang; Li Chao; Liu Sheng; Zu Qingquan; Li Linsun

    2011-01-01

    Objective: to assess the technical feasibility of implanting separating stent-graft into the canine thoracic aorta and to study its biocompatibility. Methods: Twelve adult dogs were randomly and equally divided into three groups. The right femoral artery was cut open, through which the separating stent-graft was inserted and deployed in the canine thoracic aorta, with the proximal end of the graft being quite close to the origin of the left subclavian artery. the technical feasibility of the deployment process was assessed. Angiography was performed at 4, 8 and 12 weeks after stent-graft placement to evaluate the position and patency of the stent-graft. Then the dogs were sacrificed and the specimens were collected for pathologic study. Both gross and microscopic examinations were made to evaluate the fixation of the stent-graft with the vessel wall, the endothelialization of stent-graft surface and the pathologic changes of the vascular wall. Results: A total of ten separating stent-grafts were successfully deployed in the canine thoracic aorta, no migration or deformation occurred. One dog died of massive bleeding due to the rupture of the right femoral artery which occurred when the delivery system containing the inner bare stent was inserted through the right femoral artery. Death occurred in another dog as a result of the ascending aorta rupture caused by the migration of outer-layer stent-graft. Angiography was conducted at 4, 8 and 12 weeks after stent-graft placement. No migration, deformation, rupture or stenosis of the implanted stent-grafts were observed. The formation of intima on the inner surface of the bare stent appeared at 4 weeks, which became more and more obvious with the time passing, and at 12 weeks complete endothelialization of stent-graft surface was observed. Conclusion: Technically, it is feasible to deploy the separating aortic stent-graft into the canine thoracic aorta. Moreover, the separating aortic stent-graft carries excellent

  3. Imaging cardiac activation sequence during ventricular tachycardia in a canine model of nonischemic heart failure.

    Science.gov (United States)

    Han, Chengzong; Pogwizd, Steven M; Yu, Long; Zhou, Zhaoye; Killingsworth, Cheryl R; He, Bin

    2015-01-15

    Noninvasive cardiac activation imaging of ventricular tachycardia (VT) is important in the clinical diagnosis and treatment of arrhythmias in heart failure (HF) patients. This study investigated the ability of the three-dimensional cardiac electrical imaging (3DCEI) technique for characterizing the activation patterns of spontaneously occurring and norepinephrine (NE)-induced VTs in a newly developed arrhythmogenic canine model of nonischemic HF. HF was induced by aortic insufficiency followed by aortic constriction in three canines. Up to 128 body-surface ECGs were measured simultaneously with bipolar recordings from up to 232 intramural sites in a closed-chest condition. Data analysis was performed on the spontaneously occurring VTs (n=4) and the NE-induced nonsustained VTs (n=8) in HF canines. Both spontaneously occurring and NE-induced nonsustained VTs initiated by a focal mechanism primarily from the subendocardium, but occasionally from the subepicardium of left ventricle. Most focal initiation sites were located at apex, right ventricular outflow tract, and left lateral wall. The NE-induced VTs were longer, more rapid, and had more focal sites than the spontaneously occurring VTs. Good correlation was obtained between imaged activation sequence and direct measurements (averaged correlation coefficient of ∼0.70 over 135 VT beats). The reconstructed initiation sites were ∼10 mm from measured initiation sites, suggesting good localization in such a large animal model with cardiac size similar to a human. Both spontaneously occurring and NE-induced nonsustained VTs had focal initiation in this canine model of nonischemic HF. 3DCEI is feasible to image the activation sequence and help define arrhythmia mechanism of nonischemic HF-associated VTs. Copyright © 2015 the American Physiological Society.

  4. The effects of topical mesenchymal stem cell transplantation in canine experimental cutaneous wounds

    Science.gov (United States)

    Kim, Ju-Won; Lee, Jong-Hwan; Lyoo, Young S; Jung, Dong-In; Park, Hee-Myung

    2013-01-01

    Background Adult stem cells have been widely investigated in bioengineering approaches for tissue repair therapy. We evaluated the clinical value and safety of the application of cultured bone marrow-derived allogenic mesenchymal stem cells (MSCs) for treating skin wounds in a canine model. Hypothesis Topical allogenic MSC transplantation can accelerate the closure of experimental full-thickness cutaneous wounds and attenuate local inflammation. Animals Adult healthy beagle dogs (n = 10; 3–6 years old; 7.2–13.1 kg) were studied. Methods Full-thickness skin wounds were created on the dorsum of healthy beagles, and allogenic MSCs were injected intradermally. The rate of wound closure and the degree of collagen production were analysed histologically using haematoxylin and eosin staining and trichrome staining. The degree of cellular proliferation and angiogenesis was evaluated by immunocytochemistry using proliferating cell nuclear antigen-, vimentin- and α-smooth muscle actin-specific antibodies. Local mRNA expression levels of interleukin-2, interferon-γ, basic fibroblast growth factor and matrix metalloproteinase-2 were evaluated by RT-PCR. Results Compared with the vehicle-treated wounds, MSC-treated wounds showed more rapid wound closure and increased collagen synthesis, cellular proliferation and angiogenesis. Moreover, MSC-treated wounds showed decreased expression of pro-inflammatory cytokines (interleukin-2 and interferon-γ) and wound healing-related factors (basic fibroblast growth factor and matrix metalloproteinase-2). Conclusion and clinical importance Topical transplantation of MSCs results in paracrine effects on cellular proliferation and angiogenesis, as well as modulation of local mRNA expression of several factors related to cutaneous wound healing. Résumé Contexte Les cellules souches adultes ont été largement étudiées dans les approches de bio-ingénierie pour la thérapie de réparation tissulaire. Nous évaluons l

  5. Prevention approaches in a preclinical canine model of Alzheimer’s disease: Benefits and challenges

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    Paulina R. Davis

    2014-03-01

    Full Text Available Aged dogs spontaneously develop many features of human aging and Alzheimer’s disease (AD including cognitive decline and neuropathology. In this review, we discuss age-dependent learning tasks, memory tasks, and functional measures that can be used in aged dogs for sensitive treatment outcome measures. Neuropathology that is linked to cognitive decline is described along with examples of treatment studies that show reduced neuropathology in aging dogs (dietary manipulations, behavioral enrichment, immunotherapy, and statins. Studies in canine show that multi-targeted approaches may be more beneficial than single pathway manipulations (e.g. antioxidants combined with behavioral enrichment. Aging canine studies show good predictive validity for human clinical trials outcomes (e.g. immunotherapy and several interventions tested in dogs strongly support a prevention approach (e.g. immunotherapy and statins. Further, dogs are ideally suited for prevention studies as they the age because onset of cognitive decline and neuropathology strongly support longitudinal interventions that can be completed within a 3-5 year period. Disadvantages to using the canine model are that they lengthy, use labor-intensive comprehensive cognitive testing, and involve costly housing (almost as high as that of nonhuman primates. However overall, using the dog as a preclinical model for testing preventive approaches for AD may complement work in rodents and nonhuman primates.

  6. Passaged adult chondrocytes can form engineered cartilage with functional mechanical properties: a canine model.

    Science.gov (United States)

    Ng, Kenneth W; Lima, Eric G; Bian, Liming; O'Conor, Christopher J; Jayabalan, Prakash S; Stoker, Aaron M; Kuroki, Keiichi; Cook, Cristi R; Ateshian, Gerard A; Cook, James L; Hung, Clark T

    2010-03-01

    It was hypothesized that previously optimized serum-free culture conditions for juvenile bovine chondrocytes could be adapted to generate engineered cartilage with physiologic mechanical properties in a preclinical, adult canine model. Primary or passaged (using growth factors) adult chondrocytes from three adult dogs were encapsulated in agarose, and cultured in serum-free media with transforming growth factor-beta3. After 28 days in culture, engineered cartilage formed by primary chondrocytes exhibited only small increases in glycosaminoglycan content. However, all passaged chondrocytes on day 28 elaborated a cartilage matrix with compressive properties and glycosaminoglycan content in the range of native adult canine cartilage values. A preliminary biocompatibility study utilizing chondral and osteochondral constructs showed no gross or histological signs of rejection, with all implanted constructs showing excellent integration with surrounding cartilage and subchondral bone. This study demonstrates that adult canine chondrocytes can form a mechanically functional, biocompatible engineered cartilage tissue under optimized culture conditions. The encouraging findings of this work highlight the potential for tissue engineering strategies using adult chondrocytes in the clinical treatment of cartilage defects.

  7. Biomechanical characteristics of self-ligating brackets in a vertically displaced canine model: a finite element analysis.

    Science.gov (United States)

    Kim, S-J; Kwon, Y-H; Hwang, C-J

    2016-05-01

    The objective of this study was to compare the biomechanical characteristics between two types of self-ligating brackets and conventional metal brackets using finite element analysis of a vertically displaced canine model focusing on the desired force on the canine and undesirable forces on adjacent teeth. Three-dimensional finite element models of the maxillary dentition with 1-mm, 2-mm, and 3-mm vertically displaced canines were constructed. Two different self-ligating brackets (In-Ovation C and Smart clip) and a conventional metal bracket (Micro-arch) were modeled. After a 0.016-inch NiTi (0.40 mm, round) wire was engaged, the displacement of each tooth was calculated using x-, y-, and z-coordinates, and the tensile and compressive stresses were calculated. The extrusion and maximal tensile stress of the canine differed little between the three brackets, but the intrusion and minimal compressive stress values of the adjacent teeth differed considerably and were highest in the Smart clip and least in the In-Ovation C. The extrusion and maximal tensile stress of the canine in the 3-mm displacement model was less than that in the 2-mm displacement model, and the intrusion and minimal compressive stress of the adjacent teeth increased with the degree of displacement. Self-ligating brackets were not superior to conventional brackets in leveling a vertically displaced canine. A continuous arch wire may not be recommended for leveling of severely displaced canines whether using self-ligating or conventional brackets. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Cryoplasty for the treatment of iliac artery stenosis in canine model

    International Nuclear Information System (INIS)

    Wu Zhengzhong; Yang Weizhu; Jiang Na; Zheng Qubin; Huang Keyao; Huang Ning; Shen Quan

    2013-01-01

    Objective To evaluate the treatment effect of balloon angioplasty and cryoplasty on iliac artery stenosis in canine model. Methods: Canine models of iliac artery stenosis were established with surgical ligation and transfixion. Models were randomly divided into two groups: iliac artery stenosis treated by cryoplasty (n = 8) and by balloon angioplasty (n = 8). The degree of iliac artery stenosis of two model groups was assessed by digital subtraction angiography (DSA) immediately and two weeks after the angioplasties. Then all the dogs were executed for pathological observation of the target vessels. Results: Sixteen canine models of iliac artery stenosis were established by surgical ligation and transfixion method with 100% success rate. DSA showed there was (45 ± 12)% of residual artery stenosis in the cryoplasty group immediately after surgery, while it was (39-12)% in the balloon angioplasty group, and there was no significant difference between them (t = 3.183, P > 0.05). The artery stenosis of cryoplasty group was (48 ± 17)% after two weeks and not significantly different from that after surgery immediately (t = -1.271, P > 0.05). The artery stenosis of balloon angioplasty group was (67 ± 13)% after two weeks, and it was significantly higher compared with at after surgery immediately (t = -6.666, P < 0.01). The degree of vascular stenosis in balloon angioplasty group was severer than that in cryoplasty group two weeks after angiography (P = 0.041). The pathological examination showed artery intimal hyperplasia in cryoplasty group was milder than that in balloon angioplasty group and neointimal content of collagen in cryoplasty group was less than that in balloon angioplasty group. Conclusions: The animal models of iliac artery stenosis were established successfully with surgical ligation and transfixion by damaging the intima and media of arterial wall. Compared with balloon angioplasty, the cryoplasty was able to inhibit proliferation of intimal and reduce

  9. Experimental Object-Oriented Modelling

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius

    through, e.g., technical prototyping and active user involvement. We introduce and examine “experimental object-oriented modelling” as the intersection of these practices. The contributions of this thesis are expected to be within three perspectives on models and modelling in experimental system...... development: Grounding We develop an empirically based conceptualization of modelling and use of models in system development projects characterized by a high degree of uncertainty in requirements and point to implications for tools and techniques for modelling in such a setting. Techniques We introduce......This thesis examines object-oriented modelling in experimental system development. Object-oriented modelling aims at representing concepts and phenomena of a problem domain in terms of classes and objects. Experimental system development seeks active experimentation in a system development project...

  10. Experimental adaptation of wild-type canine distemper virus (CDV to the human entry receptor CD150.

    Directory of Open Access Journals (Sweden)

    Maria Bieringer

    Full Text Available Canine distemper virus (CDV, a close relative of measles virus (MV, is widespread and well known for its broad host range. When the goal of measles eradication may be achieved, and when measles vaccination will be stopped, CDV might eventually cross the species barrier to humans and emerge as a new human pathogen. In order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors CD150 (SLAM and nectin-4 as first step to infect human target cells. Recombinant wild-type CDV-A75/17(red adapted quickly to growth in human H358 epithelial cells expressing human nectin-4. Sequencing of the viral attachment proteins (hemagglutinin, H, and fusion protein, F genes revealed that no adaptive alteration was required to utilize human nectin-4. In contrast, the virus replicated only to low titres (10(2 pfu/ml in Vero cells expressing human CD150 (Vero-hSLAM. After three passages using these cells virus was adapted to human CD150 and replicated to high titres (10(5 pfu/ml. Sequence analyses revealed that only one amino acid exchange in the H-protein at position 540 Asp→Gly (D540G was required for functional adaptation to human CD150. Structural modelling suggests that the adaptive mutation D540G in H reflects the sequence alteration from canine to human CD150 at position 70 and 71 from Pro to Leu (P70L and Gly to Glu (G71E, and compensates for the gain of a negative charge in the human CD150 molecule. Using this model system our data indicate that only a minimal alteration, in this case one adaptive mutation, is required for adaptation of CDV to the human entry receptors, and help to understand the molecular basis why this adaptive mutation occurs.

  11. A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models

    NARCIS (Netherlands)

    Y.H. Sniekers (Yvonne); F. Intema (Femke); F.P.J.G. Lafeber (Floris); G.J.V.M. van Osch (Gerjo); J.P.T.M. van Leeuwen (Hans); H.H. Weinans (Harrie); S.C. Mastbergen (Simon)

    2008-01-01

    textabstractBACKGROUND: This study evaluates changes in peri-articular bone in two canine models for osteoarthritis: the groove model and the anterior cruciate ligament transection (ACLT) model. METHODS: Evaluation was performed at 10 and 20 weeks post-surgery and in addition a 3-weeks time point

  12. Pan-nitinol occluder and special delivery device for closure of patent ductus arteriosus: a canine-model feasibility study.

    Science.gov (United States)

    Jiang, Hai-bin; Bai, Yuan; Zong, Gang-jun; Han, Lin; Li, Wei-ping; Lu, Yang; Qin, Yong-wen; Zhao, Xian-xian

    2013-01-01

    The aim of this study was to evaluate a new type of occluder for patent ductus arteriosus. Patent ductus arteriosus was established in a canine model by anastomosing a length of autologous jugular vein to the descending aorta and the left pulmonary artery in an end-to-side fashion. Transcatheter closure of each patent ductus arteriosus was performed on 10 dogs, which were then monitored for as long as 6 months with aortography, echocardiography, and histologic evaluation. Transcatheter closure with use of the novel pan-nitinol device was successful in all canine models. Postoperative echocardiography showed that the location and shape of the occluders were normal, without any residual shunting. Further histologic evaluation confirmed that the occluder surface was completely endothelialized 3 months after implantation. Transcatheter patent ductus arteriosus closure with the pan-nitinol occluder can be performed safely and successfully in a canine model and shows good biological compatibility and low mortality rates.

  13. A Canine Non-Weight-Bearing Model with Radial Neurectomy for Rotator Cuff Repair.

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    Xiaoxi Ji

    Full Text Available The major concern of using a large animal model to study rotator cuff repair is the high rate of repair retears. The purpose of this study was to test a non-weight-bearing (NWB canine model for rotator cuff repair research.First, in the in vitro study, 18 shoulders were randomized to 3 groups. 1 Full-width transections repaired with modified Mason-Allen sutures using 3-0 polyglactin suture, 2 Group 1 repaired using number 2 (#2 polyester braid and long-chain polyethylene suture, and 3 Partial-width transections leaving the superior 2 mm infraspinatus tendon intact without repair. In the in vivo study of 6 dogs, the infraspinatus tendon was partially transected as the same as the in vitro group 3. A radial neurectomy was performed to prevent weight bearing. The operated limb was slung in a custom-made jacket for 6 weeks.In the in vitro study, mean ultimate tensile load and stiffness in Group 2 were significantly higher than Group 1 and 3 (p<0.05. In the in vivo study, gross inspection and histology showed that the preserved superior 2-mm portion of the infraspinatus tendon remained intact with normal structure.Based on the biomechanical and histological findings, this canine NWB model may be an appropriate and useful model for studies of rotator cuff repair.

  14. Towards immunotherapy with redirected T cells in a large animal model: Ex vivo activation, expansion, and genetic modification of canine T cells

    Science.gov (United States)

    Mata, Melinda; Vera, Juan; Gerken, Claudia; Rooney, Cliona M.; Miller, Tasha; Pfent, Catherine; Wang, Lisa L.; Wilson-Robles, Heather M.; Gottschalk, Stephen

    2014-01-01

    Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has shown promising anti-tumor activity in early phase clinical studies, especially for hematological malignancies. However, most preclinical models do not reliably mimic human disease. We reasoned that developing an adoptive T-cell therapy approach for spontaneous osteosarcoma (OS) occurring in dogs would more closely reproduce the condition in human cancer. To generate CAR-expressing canine T cells we developed expansion and transduction protocols that allow for the generation of sufficient numbers of CAR-expressing canine T cells for future clinical studies in dogs within 2 weeks of ex vivo culture. To evaluate the functionality of CAR-expressing canine T cells we targeted HER2-positive OS. We demonstrate that canine OS is positive for HER2, and that canine T cells expressing a HER2-specific CAR with human-derived transmembrane and CD28.ζ signaling domains recognize and kill HER2-positive canine OS cell lines in an antigen-dependent manner. To reduce the potential immunogenicity of the CAR we evaluated a CAR with canine-derived transmembrane and signaling domains, and found no functional difference between human and canine CARs. Hence, we have successfully developed a strategy to generate CAR-expressing canine T cells for future preclinical studies in dogs. Testing T-cell therapies in an immunocompetent, outbred animal model may improve our ability to predict their safety and efficacy prior to conducting studies in humans. PMID:25198528

  15. Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.

    Directory of Open Access Journals (Sweden)

    Bonnie K Harrington

    Full Text Available Acalabrutinib (ACP-196 is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL. First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR was 25% (5/20 with a median progression free survival (PFS of 22.5 days. Clinical benefit was observed in 30% (6/20 of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL.

  16. The Development of a Canine Anorectal Autotransplantation Model Based on Blood Supply: A Preliminary Case Report

    Science.gov (United States)

    Nakamura, Tatsuo; Sato, Tomoyuki; Naito, Munekazu; Fujii, Satoshi; Mihara, Makoto; Koshima, Isao

    2012-01-01

    Colostomy is conventionally the only treatment for anal dysfunction. Recently, a few trials of anorectal transplantation in animals have been published; however, further development of this technique is required. Moreover, it is crucial to perform this research in dogs, which resemble humans in anorectal anatomy and biology. We designed a canine anorectal transplantation model, wherein anorectal autotransplantation was performed by anastomoses of the rectum, inferior mesenteric artery (IMA) and vein, and pudendal nerves. Resting pressure in the anal canal and anal canal pressure fluctuation were measured before and after surgery. Graft pathology was examined three days after surgery. The anal blood supply was compared with that in three beagles using indocyanine green (ICG) fluorescence angiography. The anorectal graft had sufficient arterial blood supply from the IMA; however, the graft’s distal end was congested and necrotized. Functional examination demonstrated reduced resting pressure and the appearance of an irregular anal canal pressure wave after surgery. ICG angiography showed that the pudendal arteries provided more blood flow than the IMA to the anal segment. This is the first canine model of preliminary anorectal autotransplantation, and it demonstrates the possibility of establishing a transplantation model in dogs using appropriate vascular anastomoses, thus contributing to the progress of anorectal transplantation. PMID:22970198

  17. Distribution of coronary arterial capacitance in a canine model.

    Science.gov (United States)

    Lader, A S; Smith, R S; Phillips, G C; McNamee, J E; Abel, F L

    1998-03-01

    The capacitative properties of the major left coronary arteries, left main (LM), left anterior descending (LAD), and left circumflex (LCX), were studied in 19 open-chest isolated dog hearts. Capacitance was determined by using ramp perfusion and a left ventricular-to-coronary shunt diastolic decay method; both methods gave similar results, indicating a minimal systolic capacitative component. Increased pericardial pressure (PCP), 25 mmHg, was used to experimentally alter transmural wall pressure. The response to increased PCP was different in the LAD vs. LCX; increasing PCP decreased capacitance in the LCX but increased capacitance in the LAD. This may have been due to the different intramural vs. epicardial volume distribution of these vessels and a decrease in intramural tension during increased PCP. Increased PCP decreased LCX capacitance by approximately 13%, but no changes in conductance or zero flow pressure intercept occurred in any of the three vessels, i. e., evidence against the waterfall theory of vascular collapse at these levels of PCP. Coronary arterial capacitance was also linearly related to perfusion pressure.

  18. EGFR, HER-2 and KRAS in canine gastric epithelial tumors: a potential human model?

    Directory of Open Access Journals (Sweden)

    Rossella Terragni

    Full Text Available Epidermal growth factor receptor (EGFR or HER-1 and its analog c-erbB-2 (HER-2 are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7% carcinomas were classified as intestinal-type and 9 (64.3% as diffuse-type. EGFR was overexpressed (≥ 1+ in 8 (42.1% cases and HER-2 (3+ in 11 (57.9% cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80% than in the diffuse-type (11.1%, p = 0.023. KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R. EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer.

  19. Micro-computed tomography (CT) based assessment of dental regenerative therapy in the canine mandible model

    Science.gov (United States)

    Khobragade, P.; Jain, A.; Setlur Nagesh, S. V.; Andreana, S.; Dziak, R.; Sunkara, S. K.; Sunkara, S.; Bednarek, D. R.; Rudin, S.; Ionita, C. N.

    2015-03-01

    High-resolution 3D bone-tissue structure measurements may provide information critical to the understanding of the bone regeneration processes and to the bone strength assessment. Tissue engineering studies rely on such nondestructive measurements to monitor bone graft regeneration area. In this study, we measured bone yield, fractal dimension and trabecular thickness through micro-CT slices for different grafts and controls. Eight canines underwent surgery to remove a bone volume (defect) in the canine's jaw at a total of 44 different locations. We kept 11 defects empty for control and filled the remaining ones with three regenerative materials; NanoGen (NG), a FDA-approved material (n=11), a novel NanoCalcium Sulfate (NCS) material (n=11) and NCS alginate (NCS+alg) material (n=11). After a minimum of four and eight weeks, the canines were sacrificed and the jaw samples were extracted. We used a custombuilt micro-CT system to acquire the data volume and developed software to measure the bone yield, fractal dimension and trabecular thickness. The software used a segmentation algorithm based on histograms derived from volumes of interest indicated by the operator. Using bone yield and fractal dimension as indices we are able to differentiate between the control and regenerative material (p<0.005). Regenerative material NCS showed an average 63.15% bone yield improvement over the control sample, NCS+alg showed 55.55% and NanoGen showed 37.5%. The bone regeneration process and quality of bone were dependent upon the position of defect and time period of healing. This study presents one of the first quantitative comparisons using non-destructive Micro-CT analysis for bone regenerative material in a large animal with a critical defect model. Our results indicate that Micro-CT measurement could be used to monitor invivo bone regeneration studies for greater regenerative process understanding.

  20. [Effect of benazepril on atrial cytoskeleton remodeling in the canine atrial fibrillation models].

    Science.gov (United States)

    Liu, Li; Qu, Xiu-Fen; Yu, Yang; Bai, Bing; Huang, Yong-Lin

    2009-10-20

    To investigate the effect of benazepril on atrial cytoskeleton remodeling in atrial fibrillation (AF) canines induced by chronic rapid atrial pacing (RAP). Twenty canines were randomly divided into 3 groups: (1) Sham-operated group without RAP; (2) AF group: AF established by RAP at 600 beats per minute for 6 weeks; (3) Benazepril group: benazepril was dosed from 1 week pre-pacing to 6 weeks post-pacing. The diameter of atrial cardiomyocyte was measured, collagen volume fraction (CVF) analyzed by Masson staining and the expression and distribution of desmin were assayed by immunohistochemistry. RT-PCR method was used to semi-quantify the mRNA expression of beta-tubulin and desmin. The diameter of atrial cardiomyocyte increased in AF group [LA:(27.9 +/- 3.8) microm; RA: (26.8 +/- 3.2) microm] and benazepril group[LA: (25.1 +/- 3.4) microm; RA: (25.2 +/- 3.5) microm] than sham-operated group [LA: (19.6 +/- 2.9) microm; RA: (18.7 +/- 2.6) microm] (P benazepril group than AF group [LA: (11.3 +/- 0.8)% vs (16.9 +/- 1.1)%, RA: (10.9 +/- 0.8)% vs (15.7 +/- 2.3)%, P benazepril group than AF group (P benazepril group than AF group (LA:0.8 +/- 0.4 vs 1.0 +/- 0.3, 0.7 +/- 0.3 vs 0.9 +/- 0.4; RA:0.7 +/- 0.3 vs 1.0 +/- 0.6, 0.7 +/- 0.3 vs 1.1 +/- 0.3, P Benazepril can favorably improve atrial cytoskeleton remodeling in the canine atrial fibrillation model.

  1. The effect of experimental gastric dilatation-volvulus on adenosine triphosphate content and conductance of the canine gastric and jejunal mucosa

    OpenAIRE

    Peycke, Laura E.; Hosgood, Giselle; Davidson, Jacqueline R.; Tetens, Joanne; Taylor, H. Wayne

    2005-01-01

    The objective of this study was to determine if experimental gastric dilatation volvulus (GDV) would decrease adenosine triphosphate (ATP) concentration and increase membrane conductance of the canine gastric and jejunal mucosa. Male dogs (n = 15) weighing between 20 and 30 kg were used. Dogs were randomly assigned to 1 of 3 equal groups: Group 1 was control, group 2 was GDV, and group 3 was ischemia. All dogs were anesthetized for 210 min. Group 1 had no manipulation. Group 2 had GDV experim...

  2. Animal-Assisted Therapy for persons with disabilities based on canine tail language interpretation via fuzzy emotional behavior model.

    Science.gov (United States)

    Phanwanich, Warangkhana; Kumdee, Orrawan; Ritthipravat, Panrasee; Wongsawat, Yodchanan

    2011-01-01

    Animal-Assisted Therapy (AAT) is the science that employs the merit of human-animal interaction to alleviate mental and physical problems of persons with disabilities. However, to achieve the goal of AAT for persons with severe disabilities (e.g. spinal cord injury and amyotrophic lateral sclerosis), real-time animal language interpretation is needed. Since canine behaviors can be visually distinguished from its tail, this paper proposes the automatic real-time interpretation of canine tail language for human-canine interaction in the case of persons with severe disabilities. Canine tail language is captured via two 3-axis accelerometers. Directions and frequency are selected as our features of interests. New fuzzy rules and center of gravity (COG)-based defuzzification method are proposed in order to interpret the features into three canine emotional behaviors, i.e., agitate, happy, and scare as well as its blended emotional behaviors. The emotional behavior model is performed in the simulated dog. The average recognition rate in real dog is 93.75% accuracy.

  3. Power Doppler Imaging in Acute Renal Vein Occlusion and Recanalization: a Canine Model

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, So-Young; Kim, In-One; Kim, Young-Il; Lee, Kyoung Ho; Lee, Min Woo; Youn, Byung Jae; Kim, Woo Sun; Yeon, Kyung Mo [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2008-04-15

    Objective : To evaluate the dynamic changes of the power Doppler (PD) in acute renal vein occlusion and recanalization in a canine model. Materials and Methods : We performed a PD of the kidney during graded renal vein occlusion and recanalization induced by balloon inflation and deflation in nine dogs. The PD images were transferred to a personal computer, and the PD signals were quantified. Result : We observed the temporal change of the PD signal during renal vein occlusion and recanalization, with a decrease in the PD signal during occlusion and an increase during recanalization. The mean PD signal decreased gradually as the renal vein was occluded, and conversely increased gradually with sequential relief of occlusion. The sequential change of the mean value of the PD signal was statistically significant. Conclusion : The PD can detect a change in renal blood flow during acute renal vein occlusion and recanalization in a canine model. The PD may be used as a helpful tool for the early detection of acute renal vein thrombosis and the monitoring of renal perfusion.

  4. Power Doppler Imaging in Acute Renal Vein Occlusion and Recanalization: a Canine Model

    International Nuclear Information System (INIS)

    Yoo, So-Young; Kim, In-One; Kim, Young-Il; Lee, Kyoung Ho; Lee, Min Woo; Youn, Byung Jae; Kim, Woo Sun; Yeon, Kyung Mo

    2008-01-01

    Objective : To evaluate the dynamic changes of the power Doppler (PD) in acute renal vein occlusion and recanalization in a canine model. Materials and Methods : We performed a PD of the kidney during graded renal vein occlusion and recanalization induced by balloon inflation and deflation in nine dogs. The PD images were transferred to a personal computer, and the PD signals were quantified. Result : We observed the temporal change of the PD signal during renal vein occlusion and recanalization, with a decrease in the PD signal during occlusion and an increase during recanalization. The mean PD signal decreased gradually as the renal vein was occluded, and conversely increased gradually with sequential relief of occlusion. The sequential change of the mean value of the PD signal was statistically significant. Conclusion : The PD can detect a change in renal blood flow during acute renal vein occlusion and recanalization in a canine model. The PD may be used as a helpful tool for the early detection of acute renal vein thrombosis and the monitoring of renal perfusion

  5. GIS modeling for canine dirofilariosis risk assessment in central Italy

    Directory of Open Access Journals (Sweden)

    Michele Mortarino

    2008-05-01

    Full Text Available A survey was conducted in an area of central Italy in order to study the prevalence of Dirofilaria immitis and D. repens in dogs. Blood samples were collected from 283 dogs and examined using a modified Knott’s technique. In addition, in order to detect D. immitis occult infection, 203 serum samples were also analysed for D. immitis antigen detection. The results were analyzed in order to evaluate the behavioural and attitudinal risk factors. A geographical information system (GIS for the study area was constructed, utilizing the following data layers: administrative boundaries, elevation, temperature, rainfall and humidity. Microfilariae were detected in 32 of the 283 dogs surveyed, constituting a total Dirofilaria prevalence of 11.3%. In particular, 20 dogs (7.1% were positive for D. immitis and 12 dogs (4.2% for D. repens microfilariae. One case of D. immitis occult infection was also detected. Choroplethic municipal maps were drawn within the GIS in order to display the distribution of each Dirofilaria species in the study area. Statistical analysis showed a significant association between Dirofilaria infection and animal attitude (hunting/truffle dogs showed a higher prevalence compared to guard/pet dogs. A higher prevalence was also recorded in 2 to 5-years old dogs. Furthermore a GIS-based modelling of climatic data, collected from 5 meteorological stations in the study area, was performed to estimate the yearly number of D. immitis generations in the mosquito vector. The results of the model as depicted by GIS analysis was highly concordant with the territorial distribution of positive dogs and showed that D. immitis spreading is markedly influenced by season. The potential transmission period in the study area was found to be confined to summer months with a peak in July and August, as expected for a temperate region where summer season is the most favourable period for the parasite.

  6. A canine model of Cohen syndrome: Trapped Neutrophil Syndrome.

    Science.gov (United States)

    Shearman, Jeremy R; Wilton, Alan N

    2011-05-23

    Trapped Neutrophil Syndrome (TNS) is a common autosomal recessive neutropenia in Border collie dogs. We used a candidate gene approach and linkage analysis to show that the causative gene for TNS is VPS13B. We chose VPS13B as a candidate because of similarities in clinical signs between TNS and Cohen syndrome, in human, such as neutropenia and a typical facial dysmorphism. Linkage analysis using microsatellites close to VPS13B showed positive linkage of the region to TNS. We sequenced each of the 63 exons of VPS13B in affected and control dogs and found that the causative mutation in Border collies is a 4 bp deletion in exon 19 of the largest transcript that results in premature truncation of the protein. Cohen syndrome patients present with mental retardation in 99% of cases, but learning disabilities featured in less than half of TNS affected dogs. It has been implied that loss of the alternate transcript of VPS13B in the human brain utilising an alternate exon, 28, may cause mental retardation. Mice cannot be used to test this hypothesis as they do not express the alternate exon. We show that dogs do express alternate transcripts in the brain utilising an alternate exon homologous to human exon 28. Dogs can be used as a model organism to explore the function of the alternately spliced transcript of VPS13B in the brain. TNS in Border collies is the first animal model for Cohen syndrome and can be used to study the disease aetiology.

  7. A canine model of Cohen syndrome: Trapped Neutrophil Syndrome

    Directory of Open Access Journals (Sweden)

    Shearman Jeremy R

    2011-05-01

    Full Text Available Abstract Background Trapped Neutrophil Syndrome (TNS is a common autosomal recessive neutropenia in Border collie dogs. Results We used a candidate gene approach and linkage analysis to show that the causative gene for TNS is VPS13B. We chose VPS13B as a candidate because of similarities in clinical signs between TNS and Cohen syndrome, in human, such as neutropenia and a typical facial dysmorphism. Linkage analysis using microsatellites close to VPS13B showed positive linkage of the region to TNS. We sequenced each of the 63 exons of VPS13B in affected and control dogs and found that the causative mutation in Border collies is a 4 bp deletion in exon 19 of the largest transcript that results in premature truncation of the protein. Cohen syndrome patients present with mental retardation in 99% of cases, but learning disabilities featured in less than half of TNS affected dogs. It has been implied that loss of the alternate transcript of VPS13B in the human brain utilising an alternate exon, 28, may cause mental retardation. Mice cannot be used to test this hypothesis as they do not express the alternate exon. We show that dogs do express alternate transcripts in the brain utilising an alternate exon homologous to human exon 28. Conclusion Dogs can be used as a model organism to explore the function of the alternately spliced transcript of VPS13B in the brain. TNS in Border collies is the first animal model for Cohen syndrome and can be used to study the disease aetiology.

  8. MRI of degenerative bone marrow lesions in experimental osteoarthritis of canine knee joints

    Energy Technology Data Exchange (ETDEWEB)

    Nolte-Ernsting, C.C.A. [Department of Diagnostic Radiology, University of Technology, Aachen, Pauwelsstrasse 30, D-52057 Aachen (Germany); Adam, G. [Department of Diagnostic Radiology, University of Technology, Aachen, Pauwelsstrasse 30, D-52057 Aachen (Germany); Buehne, M. [Department of Diagnostic Radiology, University of Technology, Aachen, Pauwelsstrasse 30, D-52057 Aachen (Germany); Prescher, A. [Department of Anatomy, University of Technology, Aachen (Germany); Guenther, R.W. [Department of Diagnostic Radiology, University of Technology, Aachen, Pauwelsstrasse 30, D-52057 Aachen (Germany)

    1996-07-01

    Objective. The objective of this study was to determine the value of MRI in the detection of degenerative bone marrow abnormalities in an animal osteoarthritis model. Design. In 10 dogs with experimentally induced unilateral osteoarthritis of the knee, MRI was performed using two-dimensional spin-echo (2D-SE) and three-dimensional gradient-echo (3D-GE) imaging. Contrast enhanced T1-weighted 2D-SE sequences were also obtained after injection of gadolinium-DTPA. The results were compared with the gross and histopathologic findings and with radiography. Results. Histopathologic specimens revealed 21 osteosclerotic lesions and 5 intraosseous cysts. On 2D-SE images, 24 of 26 lesions were detected, while 21 of 26 lesions were identified on 2D-GE sequences. Radiography, including conventional tomography, demonstrated 9 of 26 lesions. Regardless of the sequence weighting, all osteosclerotic lesions appeared hypointense on MRI. Signal loss in bone sclerosis resulted primarily from the reduction of intact fat marrow, the increased bone density being of secondary importance. Quantitative signal analysis allowed approximate estimation of the grade of sclerosis. On postcontrast images, sclerotic bone remained hypointense, although significant but non-specific enhancement relative to the normal fat marrow was observed. The extent of contrast enhancement did not correlate with the grade of osteosclerosis. All five cysts were readily diagnosed by MRI. Cysts displayed either central or marginal contrast enhancement within their cavities. Conclusions. MRI provides a sensitive method for the diagnosis of osteoarthritic bone abnormalities, allowing their differentiation from most non-degenerative subarticular lesions. (orig.). With 1 tab.

  9. Tolerance of the canine bladder to intraoperative radiation therapy: an experimental study

    International Nuclear Information System (INIS)

    Kinsella, T.J.; Sindelar, W.F.; DeLuca, A.M.; Barnes, M.; Tochner, Z.; Mixon, A.; Glatstein, E.

    1988-01-01

    An experimental study of bladder tolerance to intraoperative radiotherapy (IORT) was designed using a large animal model (adult American Foxhounds, weight 25-30 kg) to access acute and late radiation effects. Dogs were subjected to laparotomy where the bladder was mobilized and IORT was delivered using a 5 cm circular cone through a cystotomy incision with 12 MeV electrons. The bladder trigone including both ureteral orifices and the proximal urethra was irradiated in groups of 3 dogs with doses of 0, 20, 25, 30, 35, and 40 Gy. Dogs were followed clinically with repeat urinalysis, intravenous pyelogram (IVP), and cystometrogram at 1 month and then Q6 months for up to 4 years. One dog from each dose group was sacrificed electively at 1 and 2 years, whereas the other dog is being followed clinically for a minimum of 4 years. Complete autopsies were performed with particular attention to genitourinary and pelvic structures. No clinically detectable acute toxicity resulted from IORT to the bladder. Three of 15 IORT dogs (1 each at 25, 35, and 40 Gy) showed obstruction of a ureteral orifice with 2 dogs dying of renal failure secondary to bilateral hydronephrosis within 1-2 years of treatment. The remaining 12 IORT dogs and 3 control dogs have normal repeat IVP's and renal function with up to 4 years of follow-up. Serial cystometry demonstrates no major loss of bladder contractility or volume. At autopsy, histological changes of mucosal thinning and telangiectasia with submucosal fibrosis were confined to the IORT field and appeared dose-related. However, the bladder epithelium remained intact at all doses. The ureterovesical junction in animals receiving 20 Gy showed mild fibrosis of the lamina propria and moderate chronic inflammation. Above 20 Gy, these histological changes at the U-V junction were more pronounced with gross stenosis in 3 animals as predicted by the IVP

  10. Evaluation of oral and subcutaneous delivery of an experimental canarypox recombinant canine distemper vaccine in the Siberian polecate (Mustela eversmanni)

    Science.gov (United States)

    Wimsatt, Jeffrey; Biggins, Dean E.; Innes, Kim; Taylor, Bobbi; Garell, Della

    2003-01-01

    We assessed the safety and efficacy of an experimental canarypox-vectored recombinant canine distemper virus (CDV) subunit vaccine in the Siberian polecat (Mustela eversmanni), a close relative of the black-footed ferret, (M. nigripes), an endangered species that is highly susceptible to the virus. Siberian polecats were randomized into six treatment groups. Recombinant canine distemper vaccine was administered s.c. at three dose levels (104.5, 105.0, and 105.5 plaque-forming units [PFU] per dose) and was administered orally by spraying the vaccine into the oropharnyx at two dose levels (105.5, 108.0 PFU per dose). The sixth group of control animals was not vaccinated. For both routes of administration, two 1-ml doses of reconstituted vaccine were delivered 4 wk apart, followed by live virus challenge 3 wk after the second vaccination. During the challenge, Synder Hill test strain CDV obtained from the National Veterinary Services Laboratory in Ames, Iowa, was administered i.p. Serial blood samples for CDV serology were collected immediately before vaccination and challenge, and 10, 15, and 20 days after challenge. Clinical signs and body weights were recorded up to 32 days after challenge. The survival rate in animals receiving vaccine at the highest oral dose (108.0 PFU per dose) was 83.3%. Survival rate was 50.0% in the high s.c. and 60.0% in the medium s.c. groups. All animals in the low–s.c. dose, low–oral dose, and control groups died after exposure. Vaccine dose overall (oral and s.c.) and dose in response to s.c. administration when considered alone were significant predictors of survival (P = 0.006 and P = 0.04, respectively). Among the polecats challenged with virulent virus, those that died became sick sooner than those that survived. Animals that died lost significantly more weight during the 10 days after challenge than did animals that survived (P = 0.02). Survival rates did not differ by sex, founder female status, or breeding pedigree in any of

  11. Functional and Structural Changes in a Canine Model of Hereditary Primary Angle-Closure Glaucoma

    Science.gov (United States)

    Kecova, Helga; Harper, Matthew M.; Nilaweera, Wijitha; Kuehn, Markus H.; Kardon, Randy H.

    2010-01-01

    Purpose. To characterize functional and structural changes in a canine model of hereditary primary angle-closure glaucoma. Methods. Intraocular pressure (IOP) was evaluated with tonometry in a colony of glaucomatous dogs at 8, 15, 18, 20, and 30 months of age. Retinal function was evaluated using electroretinography (scotopic, photopic, and pattern). Examination of anterior segment structures was performed using gonioscopy and high-frequency ultrasonography (HFU). Results. A gradual rise in IOP was observed with an increase in age: 8 months, 14 mm Hg (median value); 15 months, 15.5 mm Hg; 18 months, 17.5 mm Hg; 20 months, 24 mm Hg; 30 months, 36 mm Hg. Provocative testing with mydriatic agents (tropicamide and atropine 1%) caused significant increases in IOP (35% and 50%, respectively). HFU analysis showed complete collapse of iridocorneal angles by 20 months of age. Scotopic and photopic ERG analysis did not reveal significant deficits, but pattern ERG analysis showed significantly reduced amplitudes in glaucomatous dogs (glaucoma, 3.5 ± 0.4 μV; control, 6.2 ± 0.3 μV; P = 0.004; Student's t-test). Histologic analysis revealed collapse of the iridocorneal angle, posterior bowing of the lamina cribrosa, swelling and loss of large retinal ganglion cells, increased glial reactivity, and increased thickening of the lamina cribrosa. Conclusions. Canine hereditary angle-closure glaucoma is characterized by a progressive increase in intraocular pressure, loss of optic nerve function, and retinal ganglion cell loss. PMID:19661222

  12. Renal capsule for augmentation cystoplasty in canine model: a favorable biomaterial?

    Directory of Open Access Journals (Sweden)

    Mehdi Salehipour

    2016-04-01

    Full Text Available ABSTRACT Purpose: To evaluate effectiveness of canine renal capsule for augmentation cystoplasty. Materials and Methods: Ten adult dogs participated in this study. After induction of anesthesia each animal underwent bed side urodynamic study, bladder capacity and bladder pressure was recorded. Then via mid line incision abdominal cavity was entered, right kidney was identified and its capsule was dissected. Bladder augmentation was done by anastomosing the renal capsule to the bladder. After 6 months bed side urodynamic study was performed again and changes in bladder volume and pressure were recorded. Then the animals were sacrificed and the augmented bladders were sent for histopathology evaluation. Results: Mean maximum anatomic bladder capacity before cystoplasty was 334.00±11.40cc which increased to 488.00±14.83cc post-operatively (p=0.039. Mean anatomic bladder pressure before cystoplasty was 19.00±1.58cmH2O which decreased to 12.60±1.14cmH2O post-operatively (p=0.039. Histopathology evaluation revealed epithelialization of the renal capsule with urothelium without evidence of fibrosis, collagen deposits or contracture. Conclusions: Our data shows that renal capsule is a favorable biomaterial for bladder augmentation in a canine model.

  13. The effects of implant composition on extensor tenosynovitis in a canine distal radius fracture model.

    Science.gov (United States)

    Sinicropi, Stefano M; Su, Brian W; Raia, Frank J; Parisien, May; Strauch, Robert J; Rosenwasser, Melvin P

    2005-03-01

    Dorsal plating of distal radius fractures with titanium plates has resulted in clinically observed tenosynovitis and tendon rupture. The goal of this study was to investigate whether titanium-based implants result in more extensor tendon inflammation than matched stainless-steel implants in a canine fracture model. An osteotomy was created in the distal radius of 18 beagles and fixed with 2.7-mm 4-hole plates composed of commercially pure titanium, titanium alloy (Ti-Al6-V4), or 316L stainless steel. Animals were killed at an average of 4 months. Tendon gliding was assessed by applying a force at the extensor musculotendinous junction and noting gliding. Histologic grading (mild, moderate, severe) was based on cellular hypertrophy, hyperplasia, and leukocytic infiltration. Tendons glided freely in 100% stainless-steel specimens, 75% of titanium alloy, and 43% of commercially pure titanium groups. A severe inflammatory reaction was identified in 60% of the titanium alloy (Ti-A16-V4) group, 57% of the pure titanium group, and 0% of the stainless-steel group. Dorsal plating of the canine radius with commercially pure titanium or titanium alloy implants produced a greater inflammatory peritendinous response than matched stainless-steel implants.

  14. A monograph proposing the use of canine mammary tumours as a model for the study of hereditary breast cancer susceptibility genes in humans.

    Science.gov (United States)

    Goebel, Katie; Merner, Nancy D

    2017-05-01

    Canines are excellent models for cancer studies due to their similar physiology and genomic sequence to humans, companion status and limited intra-breed heterogeneity. Due to their affliction to mammary cancers, canines can serve as powerful genetic models of hereditary breast cancers. Variants within known human breast cancer susceptibility genes only explain a fraction of familial cases. Thus, further discovery is necessary but such efforts have been thwarted by genetic heterogeneity. Reducing heterogeneity is key, and studying isolated human populations have helped in the endeavour. An alternative is to study dog pedigrees, since artificial selection has resulted in extreme homogeneity. Identifying the genetic predisposition to canine mammary tumours can translate to human discoveries - a strategy currently underutilized. To explore this potential, we reviewed published canine mammary tumour genetic studies and proposed benefits of next generation sequencing canine cohorts to facilitate moving beyond incremental advances.

  15. Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis

    Science.gov (United States)

    Shahbazi, Mehdi; Zahedifard, Farnaz; Taheri, Tahereh; Taslimi, Yasaman; Jamshidi, Shahram; Shirian, Sadegh; Mahdavi, Niousha; Hassankhani, Mehdi; Daneshbod, Yahya; Zarkesh-Esfahani, Sayyed Hamid; Papadopoulou, Barbara; Rafati, Sima

    2015-01-01

    Canine Visceral Leishmaniasis (CVL) is a major veterinary and public health problem caused by Leishmania infantum (L. infantum) in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated. Control of VL in dogs would dramatically decrease infection pressure of L. infantum for humans, since dogs are the main domestic reservoir. In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far. In this study, we vaccinated outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA and CPB without its unusual C-terminal extension (CPB-CTE) and evaluated its immunogenicity and protective immunity against L. infantum infectious challenge. We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals. Protection in dogs was also correlated with a strong DTH response and low parasite burden in the vaccinated group. Altogether, immunization with recombinant L. tarentolae A2-CPA-CPB-CTE was proven to be immunogenic and induced partial protection in dogs, hence representing a promising live vaccine candidate against CVL. PMID:26197085

  16. Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental Canine Visceral Leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Mehdi Shahbazi

    Full Text Available Canine Visceral Leishmaniasis (CVL is a major veterinary and public health problem caused by Leishmania infantum (L. infantum in many endemic countries. It is a severe chronic disease with generalized parasite spread to the reticuloendothelial system, such as spleen, liver and bone marrow and is often fatal when left untreated. Control of VL in dogs would dramatically decrease infection pressure of L. infantum for humans, since dogs are the main domestic reservoir. In the past decade, various subunits and DNA antigens have been identified as potential vaccine candidates in experimental animal models, but none has been approved for human use so far. In this study, we vaccinated outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA and CPB without its unusual C-terminal extension (CPB-CTE and evaluated its immunogenicity and protective immunity against L. infantum infectious challenge. We showed that vaccinated animals produced significantly higher levels of IgG2, but not IgG1, and also IFN-γ and TNF-α, but low IL-10 levels, before and after challenge as compared to control animals. Protection in dogs was also correlated with a strong DTH response and low parasite burden in the vaccinated group. Altogether, immunization with recombinant L. tarentolae A2-CPA-CPB-CTE was proven to be immunogenic and induced partial protection in dogs, hence representing a promising live vaccine candidate against CVL.

  17. Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior

    Directory of Open Access Journals (Sweden)

    Milcah C. Scott

    2016-12-01

    Full Text Available Osteosarcoma (OS is a heterogeneous and rare disease with a disproportionate impact because it mainly affects children and adolescents. Lamentably, more than half of patients with OS succumb to metastatic disease. Clarification of the etiology of the disease, development of better strategies to manage progression, and methods to guide personalized treatments are among the unmet health needs for OS patients. Progress in managing the disease has been hindered by the extreme heterogeneity of OS; thus, better models that accurately recapitulate the natural heterogeneity of the disease are needed. For this study, we used cell lines derived from two spontaneous canine OS tumors with distinctly different biological behavior (OS-1 and OS-2 for heterotypic in vivo modeling that recapitulates the heterogeneous biology and behavior of this disease. Both cell lines demonstrated stability of the transcriptome when grown as orthotopic xenografts in athymic nude mice. Consistent with the behavior of the original tumors, OS-2 xenografts grew more rapidly at the primary site and had greater propensity to disseminate to lung and establish microscopic metastasis. Moreover, OS-2 promoted formation of a different tumor-associated stromal environment than OS-1 xenografts. OS-2-derived tumors comprised a larger percentage of the xenograft tumors than OS-1-derived tumors. In addition, a robust pro-inflammatory population dominated the stromal cell infiltrates in OS-2 xenografts, whereas a mesenchymal population with a gene signature reflecting myogenic signaling dominated those in the OS-1 xenografts. Our studies show that canine OS cell lines maintain intrinsic features of the tumors from which they were derived and recapitulate the heterogeneous biology and behavior of bone cancer in mouse models. This system provides a resource to understand essential interactions between tumor cells and the stromal environment that drive the progression and metastatic propensity of

  18. Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior.

    Science.gov (United States)

    Scott, Milcah C; Tomiyasu, Hirotaka; Garbe, John R; Cornax, Ingrid; Amaya, Clarissa; O'Sullivan, M Gerard; Subramanian, Subbaya; Bryan, Brad A; Modiano, Jaime F

    2016-12-01

    Osteosarcoma (OS) is a heterogeneous and rare disease with a disproportionate impact because it mainly affects children and adolescents. Lamentably, more than half of patients with OS succumb to metastatic disease. Clarification of the etiology of the disease, development of better strategies to manage progression, and methods to guide personalized treatments are among the unmet health needs for OS patients. Progress in managing the disease has been hindered by the extreme heterogeneity of OS; thus, better models that accurately recapitulate the natural heterogeneity of the disease are needed. For this study, we used cell lines derived from two spontaneous canine OS tumors with distinctly different biological behavior (OS-1 and OS-2) for heterotypic in vivo modeling that recapitulates the heterogeneous biology and behavior of this disease. Both cell lines demonstrated stability of the transcriptome when grown as orthotopic xenografts in athymic nude mice. Consistent with the behavior of the original tumors, OS-2 xenografts grew more rapidly at the primary site and had greater propensity to disseminate to lung and establish microscopic metastasis. Moreover, OS-2 promoted formation of a different tumor-associated stromal environment than OS-1 xenografts. OS-2-derived tumors comprised a larger percentage of the xenograft tumors than OS-1-derived tumors. In addition, a robust pro-inflammatory population dominated the stromal cell infiltrates in OS-2 xenografts, whereas a mesenchymal population with a gene signature reflecting myogenic signaling dominated those in the OS-1 xenografts. Our studies show that canine OS cell lines maintain intrinsic features of the tumors from which they were derived and recapitulate the heterogeneous biology and behavior of bone cancer in mouse models. This system provides a resource to understand essential interactions between tumor cells and the stromal environment that drive the progression and metastatic propensity of OS. © 2016

  19. Dose-effective investigation of intraarterial r-Sak in canine model with acute cerebral infarctions

    International Nuclear Information System (INIS)

    Liu Sheng; Shi Haibin; Zhang Peng; Wang Chenghu; Zhou Chunguo; Li Linsun

    2007-01-01

    Objective: To compare the effect and complications of intraarterial thrombolysis with different doses of recombinant-staphylokinase (r-Sak) in canine model with acute cerebral infarction, and then to find out the most properly appropriate effective dose. Methods: The model with left cerebral embolism was established with interventional technique in 24 beagle adult dogs. They were randomly divided into 4 groups including control group(saline, 10 ml), group of low dose(r-Sak, 5 000 u/kg), middle dose(r-Sak, 10 000 u/kg) and high dose(r-Sak, 20 000 u/kg). Angiography and intraarterial thrombolysis were performed within 30 minutes after the embolization. Microcatheter was superselectively inserted into left carotid artery. Five hour's later with a repeated angiography at half, 1 and 2 hours after thrombolysis to observe the recanalization. Blood samples were collected at a series of time pre-and post-thrombolysis to test the plasma levels of PT, APTT and D-dimer. These canines were sacrificed, and their cerebri were taken out for pathologic study by the end of 24 hours. Results: The rates of efficacy within 2 hours after thrombolysis were 10.0% (1/10) in control group, 40.0% (4/10) in low dose group, 90.9% (10/11) in middle dose group and 100% (9/9) in high dose group. The rates of complete recanalization were 0, 10% (1/10), 36.4% (4/11) and 66.7% (6/9), correspondingly and respectively. There were statistically obvious differences between the 3 groups (P 0.05). Death occurred in 1 canine(high dose group) within 24 hours after thrombolysis with hemorrhagic lesion in parietal lobe of brain. No other severe complications ocurred. Conclusions: (1) Intraarterial thrombolysis with r-Sak within 5 hours after onset of thrombosis is effective and feasible. Intraarterial r-Sak shows strong thrombolytic effect for white thrombus including a few platelets. There is relative high rate of recanalization with no less than 10 000U/kg of r-Sak but accompanied with high risk of

  20. Radiographic, densitometric, and biomechanical effects of recombinant canine somatotropin in an unstable ostectomy gap model of bone healing in dogs

    International Nuclear Information System (INIS)

    Millis, D.L.; Wilkens, B.E.; Daniel, G.B.; Hubner, K.; Mathews, A.; Buonomo, F.C.; Patell, K.R.; Weigel, J.P.

    1998-01-01

    Objective: To determine the effect of recombinant canine somatotropin (STH) on radiographic, densitometric, and biomechanical aspects of bone healing using an unstable ostectomy gap model. Study Design: After an ostectomy of the midshaft radius, bone healing was evaluated over an 8-week period in control dogs (n = 4) and dogs receiving recombinant canine STH (n = 4). Animals Or Sample Population: Eight sexually intact female Beagle dogs, 4 to 5 years old. Methods: Bone healing was evaluated by qualitative and quantitative evaluation of serial radiographs every 2 weeks. Terminal dual-energy x-ray absorptiometry and three-point bending biomechanical testing were also performed. Results: Dogs receiving STH had more advanced radiographic healing of ostectomy sites. Bone area, bone mineral content, and bone density were two to five times greater at the ostectomy sites of treated dogs. Ultimate load at failure and stiffness were three and five times greater in dogs receiving STH. Conclusions: Using the ostectomy gap model, recombinant canine STH enhanced the radiographic, densitometric, and biomechanical aspects of bone healing in dogs. Clinical Relevance: Dogs at risk for delayed healing of fractures may benefit from treatment with recombinant canine STH

  1. Experimental canine distemper infection as a means of demonstrating latent effects of subacute lead intoxication

    Energy Technology Data Exchange (ETDEWEB)

    White, D.J.; McLeod, S.

    1976-01-01

    Observations on the response of the body to experimental infection with distemper virus in dogs previously dosed subacutely with lead have demonstrated a latent effect of lead on several body systems. Effects which indicated a relationship to earlier treatment with lead included evidence for stimulation of haemoglobin synthesis, changes to red blood cells resulting in increased destruction, increased vulnerability of the parenchymatous cells of the liver to damage, reduction in the weight of the skeleton and thyroid, an increase in weight of the thymus and brain and histopathological changes in the thymus. 21 references, 2 figures, 1 table.

  2. The mechanical consequence of failure of ossified union in attempted posterior spinal fusion. A canine model.

    Science.gov (United States)

    Stonecipher, T K; Vanderby, R; Sciammarella, C A; Lei, S S; Fisk, J R

    1983-01-01

    The mechanical behavior of pseudarthrosis in posterior spinal fusion was investigated. A canine model was developed in which an incompletely ossified posterior fusion mass was consistently produced. The spines were excised, and the motion segments were mechanically tested using a specially developed loading apparatus. Tests were performed to evaluate stiffness of the segments to loading with compression, torsion, and anterioposterior and lateral bending shear stiffness. Changes in other modes of loading were less consistent. The motion characteristics of the pseudarthrosis could not be predicted from the extent of the osseous defect noted on roentgenograms. These findings correlate clinically with the progression of curvature seen with pseudarthrosis in scoliosis surgery and the unpredictable results of pseudarthrosis in posterior fusion performed in treatment of degenerative disc disease.

  3. Mechanical analysis of congestive heart failure caused by bundle branch block based on an electromechanical canine heart model

    Energy Technology Data Exchange (ETDEWEB)

    Dou Jianhong; Xia Ling; Zhang Yu; Shou Guofa [Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027 (China); Wei Qing; Liu Feng; Crozier, Stuart [School of Information Technology and Electrical Engineering, University of Queensland, St Lucia, Brisbane, Queensland 4072 (Australia)], E-mail: xialing@zju.edu.cn

    2009-01-21

    Asynchronous electrical activation, induced by bundle branch block (BBB), can cause reduced ventricular function. However, the effects of BBB on the mechanical function of heart are difficult to assess experimentally. Many heart models have been developed to investigate cardiac properties during BBB but have mainly focused on the electrophysiological properties. To date, the mechanical function of BBB has not been well investigated. Based on a three-dimensional electromechanical canine heart model, the mechanical properties of complete left and right bundle branch block (LBBB and RBBB) were simulated. The anatomical model as well as the fiber orientations of a dog heart was reconstructed from magnetic resonance imaging (MRI) and diffusion tensor MRI (DT-MRI). Using the solutions of reaction-diffusion equations and with a strategy of parallel computation, the asynchronous excitation propagation and intraventricular conduction in BBB was simulated. The mechanics of myocardial tissues were computed with time-, sarcomere length-dependent uniaxial active stress initiated at the time of depolarization. The quantification of mechanical intra- and interventricular asynchrony of BBB was then investigated using the finite-element method with an eight-node isoparametric element. The simulation results show that (1) there exists inter- and intraventricular systolic dyssynchrony during BBB; (2) RBBB may have more mechanical synchrony and better systolic function of the left ventricle (LV) than LBBB; (3) the ventricles always move toward the early-activated ventricle; and (4) the septum experiences higher stress than left and right ventricular free walls in BBB. The simulation results validate clinical and experimental recordings of heart deformation and provide regional quantitative estimates of ventricular wall strain and stress. The present work suggests that an electromechanical heart model, incorporating real geometry and fiber orientations, may be helpful for better

  4. The significance of periventricular lucency on computed tomography: experimental study with canine hydrocephalus

    International Nuclear Information System (INIS)

    Murata, T.; Handa, H.; Mori, K.; Nakano, Y.

    1981-01-01

    In order to investigate the pathogenesis of periventricular lucency (PVL) in hydrocephalus, CT scans were performed with monitoring of the epidural pressure in a series of dogs with hydrocephalus induced with kaolin. PVL of various degrees was detected in the experimental animals, which disappeared immediately after a shunting operation. Correlations have been attempted between PVL on CT scans and histological examinations, contrast enhancement studies, metrizamide ventriculography, and measurement of regional cerebral blood flow in the periventricular white matter. PVL in hydrocephalus is considered to represent acute edema or chronic CSF retention in the periventricular white matter caused by an increase of water content. In other words, it is regarded as a sign of existing or preceding intraventricular hypertension on CT scan, and seems to be a reversible phenomenon to some extent. PVL may therefore become an indication for a shunt. (orig.)

  5. PEMFC modeling and experimental validation

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, J.V.C. [Federal University of Parana (UFPR), Curitiba, PR (Brazil). Dept. of Mechanical Engineering], E-mail: jvargas@demec.ufpr.br; Ordonez, J.C.; Martins, L.S. [Florida State University, Tallahassee, FL (United States). Center for Advanced Power Systems], Emails: ordonez@caps.fsu.edu, martins@caps.fsu.edu

    2009-07-01

    In this paper, a simplified and comprehensive PEMFC mathematical model introduced in previous studies is experimentally validated. Numerical results are obtained for an existing set of commercial unit PEM fuel cells. The model accounts for pressure drops in the gas channels, and for temperature gradients with respect to space in the flow direction, that are investigated by direct infrared imaging, showing that even at low current operation such gradients are present in fuel cell operation, and therefore should be considered by a PEMFC model, since large coolant flow rates are limited due to induced high pressure drops in the cooling channels. The computed polarization and power curves are directly compared to the experimentally measured ones with good qualitative and quantitative agreement. The combination of accuracy and low computational time allow for the future utilization of the model as a reliable tool for PEMFC simulation, control, design and optimization purposes. (author)

  6. Authentication of Primordial Characteristics of the CLBL-1 Cell Line Prove the Integrity of a Canine B-Cell Lymphoma in a Murine In Vivo Model

    OpenAIRE

    Rütgen, Barbara C.; Willenbrock, Saskia; Reimann-Berg, Nicola; Walter, Ingrid; Fuchs-Baumgartinger, Andrea; Wagner, Siegfried; Kovacic, Boris; Essler, Sabine E.; Schwendenwein, Ilse; Nolte, Ingo; Saalmüller, Armin; Escobar, Hugo Murua

    2012-01-01

    Cell lines are key tools in cancer research allowing the generation of neoplasias in animal models resembling the initial tumours able to mimic the original neoplasias closely in vivo. Canine lymphoma is the major hematopoietic malignancy in dogs and considered as a valuable spontaneous large animal model for human Non-Hodgkin's Lymphoma (NHL). Herein we describe the establishment and characterisation of an in vivo model using the canine B-cell lymphoma cell line CLBL-1 analysing the stabilit...

  7. Experimental Modeling of Dynamic Systems

    DEFF Research Database (Denmark)

    Knudsen, Morten Haack

    2006-01-01

    An engineering course, Simulation and Experimental Modeling, has been developed that is based on a method for direct estimation of physical parameters in dynamic systems. Compared with classical system identification, the method appears to be easier to understand, apply, and combine with physical...

  8. Exenatide Treatment Alone Improves β-Cell Function in a Canine Model of Pre-Diabetes.

    Directory of Open Access Journals (Sweden)

    Viorica Ionut

    Full Text Available Exenatide's effects on glucose metabolism have been studied extensively in diabetes but not in pre-diabetes.We examined the chronic effects of exenatide alone on glucose metabolism in pre-diabetic canines.After 10 weeks of high-fat diet (HFD, adult dogs received one injection of streptozotocin (STZ, 18.5 mg/kg. After induction of pre-diabetes, while maintained on HFD, animals were randomized to receive either exenatide (n = 7 or placebo (n = 7 for 12 weeks. β-Cell function was calculated from the intravenous glucose tolerance test (IVGTT, expressed as the acute insulin response, AIRG, the oral glucose tolerance test (OGTT, insulinogenic index and the graded-hyperglycemic clamp (clamp insulinogenic index. Whole-body insulin sensitivity was assessed by the IVGTT. At the end of the study, pancreatic islets were isolated to assess β-cell function in vitro.OGTT: STZ caused an increase in glycemia at 120 min by 22.0% (interquartile range, IQR, 31.5% (P = 0.011. IVGTT: This protocol also showed a reduction in glucose tolerance by 48.8% (IQR, 36.9% (P = 0.002. AIRG decreased by 54.0% (IQR, 40.7% (P = 0.010, leading to mild fasting hyperglycemia (P = 0.039. Exenatide, compared with placebo, decreased body weight (P<0.001 without altering food intake, fasting glycemia, insulinemia, glycated hemoglobin A1c, or glucose tolerance. Exenatide, compared with placebo, increased both OGTT- (P = 0.040 and clamp-based insulinogenic indexes (P = 0.016, improved insulin secretion in vitro (P = 0.041, but had no noticeable effect on insulin sensitivity (P = 0.405.In pre-diabetic canines, 12-week exenatide treatment improved β-cell function but not glucose tolerance or insulin sensitivity. These findings demonstrate partial beneficial metabolic effects of exenatide alone on an animal model of pre-diabetes.

  9. Evaluation of type II thyroplasty on phonatory physiology in an excised canine larynx model

    Science.gov (United States)

    Devine, Erin E.; Hoffman, Matthew R.; McCulloch, Timothy M.; Jiang, Jack J.

    2016-01-01

    Objective Type II thyroplasty is an alternative treatment for spasmodic dysphonia, addressing hyperadduction by incising and lateralizing the thyroid cartilage. We quantified the effect of lateralization width on phonatory physiology using excised canine larynges. Methods Normal closure, hyperadduction, and type II thyroplasty (lateralized up to 5mm at 1mm increments with hyperadducted arytenoids) were simulated in excised larynges (N=7). Aerodynamic, acoustic, and videokymographic data were recorded at three subglottal pressures relative to phonation threshold pressure (PTP). One-way repeated measures ANOVA assessed effect of condition on aerodynamic parameters. Random intercepts linear mixed effects models assessed effects of condition and subglottal pressure on acoustic and videokymographic parameters. Results PTP differed across conditions (p<0.001). Condition affected percent shimmer (p<0.005) but not percent jitter. Both pressure (p<0.03) and condition (p<0.001) affected fundamental frequency. Pressure affected vibratory amplitude (p<0.05) and intra-fold phase difference (p<0.05). Condition affected phase difference between the vocal folds (p<0.001). Conclusions Hyperadduction increased PTP and worsened perturbation compared to normal, with near normal physiology restored with 1mm lateralization. Further lateralization deteriorated voice quality and increased PTP. Acoustic and videokymographic results indicate that normal physiologic relationships between subglottal pressure and vibration are preserved at optimal lateralization width, but then degrade with further lateralization. The 1mm optimal width observed here is due to the small canine larynx size. Future human trials would likely demonstrate a greater optimal width, with patient-specific value potentially determined based on larynx size and symptom severity. PMID:27223665

  10. Chest wall reconstruction in a canine model using polydioxanone mesh, demineralized bone matrix and bone marrow stromal cells.

    Science.gov (United States)

    Tang, Hua; Xu, Zhifei; Qin, Xiong; Wu, Bin; Wu, Lihui; Zhao, XueWei; Li, Yulin

    2009-07-01

    Extensive chest wall defect reconstruction remains a challenging problem for surgeons. In the past several years, little progress has been made in this area. In this study, a biodegradable polydioxanone (PDO) mesh and demineralized bone matrix (DBM) seeded with osteogenically induced bone marrow stromal cells (BMSCs) were used to reconstruct a 6 cm x 5.5 cm chest wall defect. Four experimental groups were evaluated (n=6 per group): polydioxanone (PDO) mesh/DBMs/BMSCs group, polydioxanone (PDO) mesh/DBMs group, polydioxanone (PDO) mesh group, and a blank group (no materials) in a canine model. All the animals survived except those in the blank group. In all groups receiving biomaterial implants, the polydioxanone (PDO) mesh completely degraded at 24 weeks and was replaced by fibrous tissue with thickness close to that of the normal intercostal tissue (P>0.05). In the polydioxanone (PDO) mesh/DBMs/BMSCs group, new bone formation and bone-union were observed by radiographic and histological examination. More importantly, the reconstructed rib could maintain its original radian and achieve satisfactory biomechanics close to normal ribs in terms of bending stress (P>0.05). However, in the other two groups, fibrous tissue was observed in the defect and junctions, and the reconstructed ribs were easily distorted under an outer force. Based on these results, a surgical approach utilizing biodegradable polydioxanone (PDO) mesh in combination with DBMs and BMSCs could repair the chest wall defect not only in function but also in structure.

  11. Beneficial hemodynamic effects of nicorandil in a canine model of acute congestive heart failure: comparison with nitroglycerin and cromakalim.

    Science.gov (United States)

    Noguchi, K; Matsuzaki, T; Ojiri, Y; Koyama, T; Nakasone, J; Sakanashi, M

    1998-01-01

    Comparative hemodynamic effects of nicorandil (NCR), nitroglycerin (NTG) and cromakalim (CRM) were examined in a canine model of acute congestive heart failure (CHF). CHF was produced by injections of saponin into coronary arteries of anesthetized dogs followed by volume loading and continuous i.v. infusion of methoxamine. After the treatment, aortic blood flow (AoF), left ventricular dP/dt and myocardial segment shortening (SS) markedly decreased, while the left ventricular end-diastolic pressure (LVEDP), the right atrial pressure (RAP) and the systemic vascular resistance (SVR) increased. NCR (n = 6), NTG (n = 6) and CRM (n = 8), which were administered i.v. after production of CHF, caused a comparable reduction in LVEDP. NCR and CRM profoundly increased AoF and SS but NTG did only slightly. On the other hand, NTG and NCR but not CRM significantly reduced RAP. Intracoronary NCR (n = 8) exerted no or similar effects on SS as well as systemic hemodynamic indices to those observed with i.v. NCR despite distinct coronary vasodilation. These results indicate that NCR may exert beneficial hemodynamic effects in an experimental CHF mainly due to lessening both afterload and preload rather than the coronary vasodilating effect.

  12. In vivo biomechanical evaluation of a novel angle-stable interlocking nail design in a canine tibial fracture model.

    Science.gov (United States)

    Déjardin, Loïc M; Cabassu, Julien B; Guillou, Reunan P; Villwock, Mark; Guiot, Laurent P; Haut, Roger C

    2014-03-01

    To compare clinical outcome and callus biomechanical properties of a novel angle stable interlocking nail (AS-ILN) and a 6 mm bolted standard ILN (ILN6b) in a canine tibial fracture model. Experimental in vivo study. Purpose-bred hounds (n = 11). A 5 mm mid-diaphyseal tibial ostectomy was stabilized with an AS-ILN (n = 6) or an ILN6b (n = 5). Orthopedic examinations and radiographs were performed every other week until clinical union (18 weeks). Paired tibiae were tested in torsion until failure. Callus torsional strength and toughness were statistically compared and failure mode described. Total and cortical callus volumes were computed and statistically compared from CT slices of the original ostectomy gap. Statistical significance was set at P dogs (P dogs by 10 weeks and in 3/5 ILN6b dogs at 18 weeks. Callus mechanical properties were significantly greater in AS-ILN than ILN6b specimens by 77% (failure torque) and 166% (toughness). Failure occurred by acute spiral (control and AS-ILN) or progressive transverse fractures (ILN6b). Cortical callus volume was 111% greater in AS-ILN than ILN6b specimens (P < .05). Earlier functional recovery, callus strength and remodeling suggest that the AS-ILN provides a postoperative biomechanical environment more conducive to bone healing than a comparable standard ILN. © Copyright 2014 by The American College of Veterinary Surgeons.

  13. Poly-lactic-acid coating of endovascular stents: preliminary results in canine experimental av-fistulae

    Energy Technology Data Exchange (ETDEWEB)

    Schellhammer, F. [Freiburg Univ. (Germany). Dept. of Neuroradiology; Koeln Univ. (Germany). Dept. of Radiology; Berlis, A. [Bonn Univ. (Germany). Dept. of Radiology; Bloss, H.G. [Freiburg Univ. (Germany). Dept. of Neurosurgery; Pagenstecher, A. [Freiburg Univ. (Germany). Dept. of Neuropathology; Schumacher, M. [Freiburg Univ. (Germany). Dept. of Neuroradiology

    2001-02-01

    Poly-Lactic-Acid (PLA) was evaluated for coating of vascular endoprotheses in the treatment of experimental arterio-venous-fistulae (AVF). Bilateral carotid-external jugular AVF were created in 5 adult dogs. 7 PLA coated nitinol stents were placed via a transfemoral approach covering 5 AVF. The contralateral AVF remained untreated. Angiography was performed immediately after stent placement, at weeks 1 and 3 and at months 3, 6 and 9. All grafts were removed and underwent histologic examination. In 2 cases the occlusion of the AVF was successful, while misplacement occurred in 3 cases. Occlusion of the parent vessel was disclosed in 3 cases. Histologic examination revealed a mild inflammatory reaction with the presence of macrophages. There was no foreign-body reaction or fragmentation of the arterial vessel wall. PLA, which is a well-known biodegradable material, showed a good mid-term biocompatibility. Elastic mismatch of the non-elastic coating and the self-expandable nitinol stent caused misplacement. Frequent vessel-occlusions were probably due to PLA-filaments fraying into the vessel lumen. Using a different textile structure PLA might be a material suitable for coating endovascular stents. (orig.) [German] In der vorliegenden Arbeit wurden mit Poly-Laktid ummantelte Gefaessprothesen in der Behandlung von experimentell angelegten arterio-venoesen Gefaesskurzschluessen getestet. Gefaesskurzschlussverbindungen der Halsarterien mit der parallel dazu verlaufenden, tiefen Halsvene wurden in 5 Hunden operativ angelegt. 7 mit Poly-Laktid ummantelte Gefaessprothesen aus Nitinol wurden in jeweils eine Halsarterie implantiert, so dass die Gefaesskurzschlussverbindungen vollstaendig ueberdeckt war. Die gegenueberliegende Seite verblieb als Kontrolle unbehandelt. Radiologische Gefaessdarstellungen erfolgten unmittelbar nach Implantation der Gefaessprothese, nach 1 und 3 Wochen sowie nach 3, 6 und 9 Monaten. Alle Prothesen wurden operativ entfernt und feingeweblich

  14. NS5806 partially restores action potential duration but fails to ameliorate calcium transient dysfunction in a computational model of canine heart failure

    DEFF Research Database (Denmark)

    Maleckar, Mary M; Lines, Glenn T; Koivumäki, Jussi T

    2014-01-01

    AIMS: The study investigates how increased Ito, as mediated by the activator NS5806, affects excitation-contraction coupling in chronic heart failure (HF). We hypothesized that restoring spike-and-dome morphology of the action potential (AP) to a healthy phenotype would be insufficient to restore...... the intracellular Ca(2) (+) transient (CaT), due to HF-induced remodelling of Ca(2+) handling. METHODS AND RESULTS: An existing mathematical model of the canine ventricular myocyte was modified to incorporate recent experimental data from healthy and failing myocytes, resulting in models of both healthy and HF...... ionic processes with a focus on calcium transients (CaT), how these were altered in HF across the ventricular wall, and the subsequent effects of varying compound concentration in HF. Heart failure model variants recapitulated a characteristic increase in AP duration (APD) in the disease...

  15. Novel therapeutic approach for pulmonary emphysema using gelatin microspheres releasing basic fibroblast growth factor in a canine model.

    Science.gov (United States)

    Chang, Sung Soo; Yokomise, Hiroyasu; Matsuura, Natsumi; Gotoh, Masashi; Tabata, Yasuhiko

    2014-08-01

    The prognosis of patients with emphysema is poor as there is no truly effective treatment. Our previous study showed that the alveolar space was smaller and the microvessel density was higher in a canine emphysema model after the intrapulmonary arterial administration of gelatin microspheres slowly releasing basic fibroblast growth factor (bFGF-GMS). In the present study, we evaluated the functional effect of injecting bFGF-GMS via the pulmonary artery in this canine pulmonary emphysema model. Using the porcine pancreatic elastase (PPE)-induced total emphysema model, we approximated the value of lung compliance with a Power Lab System, and performed blood gas analysis in a control group, a total emphysema group, and a bFGF group in which bFGF-GMS were injected toward the whole pulmonary artery via the femoral vein. Each group comprised five dogs. Lung compliance was higher in the total emphysema group than in the control group (p = 0.031), and the bFGF group showed no significant improvement of lung compliance vs. the total emphysema group (p = 0.112). PaO2 (partial pressure of oxygen in arterial blood) was improved by administering bFGF-GMS in the total emphysema model (p = 0.027). In the canine total emphysema model, blood gas parameters were improved by the whole pulmonary arterial administration of bFGF-GMS. This method has the potential to be an effective novel therapy for pulmonary emphysema.

  16. Neonatal tolerance induction enables accurate evaluation of gene therapy for MPS I in a canine model.

    Science.gov (United States)

    Hinderer, Christian; Bell, Peter; Louboutin, Jean-Pierre; Katz, Nathan; Zhu, Yanqing; Lin, Gloria; Choa, Ruth; Bagel, Jessica; O'Donnell, Patricia; Fitzgerald, Caitlin A; Langan, Therese; Wang, Ping; Casal, Margret L; Haskins, Mark E; Wilson, James M

    2016-09-01

    High fidelity animal models of human disease are essential for preclinical evaluation of novel gene and protein therapeutics. However, these studies can be complicated by exaggerated immune responses against the human transgene. Here we demonstrate that dogs with a genetic deficiency of the enzyme α-l-iduronidase (IDUA), a model of the lysosomal storage disease mucopolysaccharidosis type I (MPS I), can be rendered immunologically tolerant to human IDUA through neonatal exposure to the enzyme. Using MPS I dogs tolerized to human IDUA as neonates, we evaluated intrathecal delivery of an adeno-associated virus serotype 9 vector expressing human IDUA as a therapy for the central nervous system manifestations of MPS I. These studies established the efficacy of the human vector in the canine model, and allowed for estimation of the minimum effective dose, providing key information for the design of first-in-human trials. This approach can facilitate evaluation of human therapeutics in relevant animal models, and may also have clinical applications for the prevention of immune responses to gene and protein replacement therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. A Canine Arthroscopic Anterior Cruciate Ligament Reconstruction Model for Study of Synthetic Augmentation of Tendon Allografts.

    Science.gov (United States)

    Cook, James L; Smith, Pat; Stannard, James P; Pfeiffer, Ferris; Kuroki, Keiichi; Bozynski, Chantelle C; Cook, Cristi

    2017-09-01

    Novel graft types, fixation methods, and means for augmenting anterior cruciate ligament (ACL) reconstructions require preclinical validation prior to safe and effective clinical application. The objective of this study was to describe and validate a translational canine model for all-inside arthroscopic complete ACL reconstruction using a quadriceps tendon allograft with internal brace (QTIB). With institutional approval, adult research hounds underwent complete transection of the native ACL followed by all-inside ACL reconstruction using the novel QTIB construct with suspensory fixation ( n  = 10). Contralateral knees were used as nonoperated controls ( n  = 10). Dogs were assessed over a 6-month period using functional, diagnostic imaging, gross, biomechanical, and histologic outcome measures required for preclinical animal models. Study results suggest that the novel QTIB construct used for complete ACL reconstruction can provide sustained knee stability and function without the development of premature osteoarthritis in a rigorous and valid preclinical model. The unique configuration of the QTIB construct-the combination of a tendon allograft with a synthetic suture tape internal brace-allowed for an effective biologic-synthetic load-sharing ACL construct. It prevented early failure, allowed for direct, four-zone graft-to-bone healing, and functional graft remodeling while avoiding problems noted with use of all-synthetic grafts. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  18. Canine periodontitis: the dog as an important model for periodontal studies.

    Science.gov (United States)

    Albuquerque, Carlos; Morinha, Francisco; Requicha, João; Martins, Teresa; Dias, Isabel; Guedes-Pinto, Henrique; Bastos, Estela; Viegas, Carlos

    2012-03-01

    Periodontal disease (PD) refers to a group of inflammatory diseases caused by bacterial plaque in the periodontium and ranges from an early stage (gingivitis) to an advanced stage (periodontitis). It is a multifactorial disease that results from the interaction of the host defence mechanisms with the plaque microorganisms. Early detection, diagnosis and treatment are essential in the control of this disease. PD has an enormous impact on human and veterinary medicine due to its high prevalence. The most common animal PD models use dogs and non-human primates, although other animals (rats, mice, hamsters, rabbits, miniature pigs, ferrets, and sheep) have also been employed. Dog models have contributed significantly to the current understanding of periodontology. The most important clinical aspects of canine PD are considered in this review and the various animal models are examined with an emphasis on the role of the dog as the most useful approach for understanding human PD and in the development of new therapeutic and preventive measures. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Adeno-Associated Virus-Mediated Correction of a Canine Model of Glycogen Storage Disease Type Ia

    OpenAIRE

    Weinstein, David A.; Correia, Catherine E.; Conlon, Thomas; Specht, Andrew; Verstegen, John; Onclin-Verstegen, Karine; Campbell-Thompson, Martha; Dhaliwal, Gurmeet; Mirian, Layla; Cossette, Holly; Falk, Darin J.; Germain, Sean; Clement, Nathalie; Porvasnik, Stacy; Fiske, Laurie

    2010-01-01

    This study by the groups of Drs. Barry Byrne and Cathryn Mah at the University of Florida examines the safety and efficacy of AAV-mediated gene delivery in a canine model of glycogen storage disease type Ia (GSDIa). The authors find that intraportal delivery of AAV8 encoding glucose-6-phosphatase-α (G6Pase) followed 20 weeks later by intraportal administration of AAV1 encoding G6Pase led to significant correction of the GSDIa phenotype.

  20. Application of a canine 238Pu dosimetry model to human bioassay data

    Energy Technology Data Exchange (ETDEWEB)

    Hickman, Jr., A. W. [Florida Univ., Gainesville, FL (United States)

    1991-08-01

    Associated with the use of 2238Pu in thermoelectric power sources for space probes and power supplies for cardiac devices is the potential for human exposure to 238Pu, primarily by inhalation. In the event of human internal exposure, a means is needed for assessing the level of intake and calculating radiation doses. Several bioassay/dosimetry models have been developed for 239Pu. However, results from studies with laboratory animals have indicated that the biokinetics, and therefore the descriptive models, of 238Pu are significantly different from those for 239Pu. A canine model accounting for these differences has been applied in this work to urinary excretion data from seven humans occupationally exposed to low levels of an insoluble 238Pu compound. The modified model provides a good description of the urinary excretion kinetics observed in the exposed humans. The modified model was also used to provide estimates of the initial intakes of 238Pu for the seven individuals; these estimates ranged from 4.5 nCi (170 Bq) to 87 nCi (3200 Bq). Autopsy data on the amount and distribution of 238Pu retained in the organs may be used in the future to validate or refute both these estimates and the assumptions used to formulate the human model. Modification of the human model to simulate an injection exposure to 239Pu gave patterns of retention in the organs and urinary excretion comparable to those seen previously in humans; further modification of the model using fecal data (unavailable for the subjects of this study) is indicated.

  1. DSA-guided embolization in establishing different canine spinal cord ischemia models and relevant diffusion-weighted imaging study

    International Nuclear Information System (INIS)

    Zhang Jingsong; Sun Lijun; Huan Yi; He Hongde; Zhang Xuexin; Zhao Haitao; Zhang Jing; Zhang Xijing

    2006-01-01

    Objective: To evaluate DSA-guided embolization in establishing different spinal cord ischemia models of canine and relevant diffusion-weighted imaging (DWI) application. Methods: Nine canines were randomly divided into three groups with different matching of lipiodol and diatrizoate meglumine which were injected into bilateral intercostal arteries at 9-11 level guided by DSA monitor. Then observe the changes of motor function and pathologic findings, especially perform routine MRI and DWI by a 1.5 T MR system. Results: Except one case, 8 embolization models were established successfully. Among three groups, slight-group got slight injury and muscle power was about 3-5 grade and range of injury was about two vertebra distance; medium-group presented obvious paraplegia and muscle power was 0-1 grade and range of injury was between 3-4 vertebra distance; severe-group showed greater severity and larger range of injury. All lesions presented high signals at routine MRI and DWI. Conclusion: Using different matching of lipiodol and diatrizoate meglumine can establish different spinal cord ischemia models of canine by DSA- guided embolization and DWI can be performed successfully by 1.5 T MR system, which may be a good method for advanced study of spinal cord ischemia. (authors)

  2. Establishment of a canine model of human type 2 diabetes mellitus by overexpressing phosphoenolypyruvate carboxykinase.

    Science.gov (United States)

    Jeong, Yeon Woo; Lee, Geun-Shik; Kim, Joung Joo; Park, Sun Woo; Ko, Kyeong Hee; Kang, Mina; Kim, Yu Kyung; Jung, Eui-Man; Hyun, Sang Hwan; Shin, Taeyoung; Jeung, Eui-Bae; Hwang, Woo Suk

    2012-08-01

    Dogs are useful models for studying human metabolic diseases such as type 2 diabetes mellitus due to similarities in physiology, anatomy and life styles with humans. Somatic cell nuclear transfer (SCNT) facilitates the production of transgenic dogs. In this study, we generated transgenic dogs expressing the phosphoenolpyruvate carboxykinase (PEPCK) gene, which is closely involved in the pathogenesis of type 2 diabetes mellitus. In addition, we assessed the cloning efficiency associated with adult or fetal (cloned or natural mating) fibroblasts as a nuclear source. Cloning efficiency was determined by the fusion, pregnancy and cloning rates. The fusion rates were significantly high for fibroblasts from cloned fetuses, but the pregnancy and cloning rates were relatively high for cells from normal fetuses. Based on these data, fetal fibroblasts were selected as the nuclear donor for SCNT and genetically engineered to overexpress the PEPCK gene and dual selection marker genes controlled by the PEPCK promoter. The transgenic cells were introduced into oocytes and transferred into five recipient dogs, resulting in two pregnancies. Finally, three puppies were born and confirmed by microsatellite analysis to be genetically identical to the donor. One puppy successfully overexpressed PEPCK mRNA and protein in the liver. This canine disease model may be useful for studying the pathogenesis and/or therapeutic targets of type 2 diabetes mellitus.

  3. Interleukin-12 Inhibits Tumor Growth in a Novel Angiogenesis Canine Hemangiosarcoma Xenograft Model

    Directory of Open Access Journals (Sweden)

    Nasim Akhtar

    2004-03-01

    Full Text Available We established a canine hemangiosarcoma cell line derived from malignant endothelial cells comprising a spontaneous tumor in a dog to provide a renewable source of endothelial cells for studies of angiogenesis in malignancy. Pieces of the hemangiosarcoma biopsy were engrafted subcutaneously in a bg/nu/XID mouse allowing the tumor cells to expand in vivo. A cell line, SB-HSA, was derived from the xenograft. SB-HSA cells expressed vascular endothelial growth factor (VEGF receptors 1 and 2, CD31, CD146, and αvβ3 integrin, and produced several growth factors and cytokines, including VEGF, basic fibroblast growth factor, and interleukin (IL-8 that are stimulatory to endothelial cell growth. These results indicated that the cells recapitulated features of mitotically activated endothelia. In vivo, SB-HSA cells stimulated robust angiogenic responses in mice and formed tumor masses composed of aberrant vascular channels in immunocompromised mice providing novel opportunities for investigating the effectiveness of antiangiogenic agents. Using this model, we determined that IL-12, a cytokine with both immunostimulatory and antiangiogenic effects, suppressed angiogenesis induced by, and tumor growth of, SB-HSA cells. The endothelial cell model we have described offers unique opportunities to pursue further investigations with IL-12, as well as other antiangiogenic approaches in cancer therapy.

  4. Establishing an in vivo model of canine prostate carcinoma using the new cell line CT1258

    International Nuclear Information System (INIS)

    Fork, Melani AM; Bullerdiek, Jörn; Nolte, Ingo; Escobar, Hugo Murua; Soller, Jan T; Sterenczak, Katharina A; Willenbrock, Saskia; Winkler, Susanne; Dorsch, Martina; Reimann-Berg, Nicola; Hedrich, Hans J

    2008-01-01

    Prostate cancer is a frequent finding in man. In dogs, malignant disease of the prostate is also of clinical relevance, although it is a less common diagnosis. Even though there are numerous differences in origin and development of the disease, man and dog share many similarities in the pathological presentation. For this reason, the dog might be a useful animal model for prostate malignancies in man. Although prostate cancer is of great importance in veterinary medicine as well as in comparative medicine, there are only few cell lines available. Thus, it was the aim of the present study to determine whether the formerly established prostate carcinoma cell line CT1258 is a suitable tool for in vivo testing, and to distinguish the growth pattern of the induced tumours. For characterisation of the in vivo behaviour of the in vitro established canine prostate carcinoma cell line CT1258, cells were inoculated in 19 NOD.CB17-Prkdc Scid /J (in the following: NOD-Scid) mice, either subcutaneously or intraperitoneally. After sacrifice, the obtained specimens were examined histologically and compared to the pattern of the original tumour in the donor. Cytogenetic investigation was performed. The cell line CT 1258 not only showed to be highly tumourigenic after subcutaneous as well as intraperitoneal inoculation, but also mimicked the behaviour of the original tumour. Tumours induced by inoculation of the cell line CT1258 resemble the situation in naturally occurring prostate carcinoma in the dog, and thus could be used as in vivo model for future studies

  5. Experimental evaluation of a new retrievable inferior vena cava filter for protection from acute pulmonary embolism in canine

    International Nuclear Information System (INIS)

    Zhou Chungao; Shi Haibing; Liu Sheng; Wang Chenghu; Liu Hairi; Li Linsun

    2007-01-01

    Objective: To evaluate the validity, safety and feasibility of a new retrieval inferior vena cava filter for the prevention of pulmonary embolism in an animal model. Methods: The model of deep iliofemoral venous thrombosis was established in 12 experimental dogs. In control group(6 experimental dogs), the deep venous thrombosis was made to fall off directly. In experimental group (6 experimental dogs), the deep venous thrombosis was made to fall off with an implanted filter in inferior vena cava. The filter's thrombus-trapping efficacy was evaluated by angiography of pulmonary artery, measurement of the mean pressure of pulmonary artery and arterial oxygen saturation before and after the deep venous thrombus falling off. Results: All filters implanted in the experimental dogs could successfully capture clot coming from deep venous thrombosis. There was no case of pulmonary embolism in experimental groups. On the other hand, pulmonary embolism occurred following the fall of deep venous thrombus in all dogs of control group. Conclusion: The retrievable inferior vena cava filter can effectively prevent from the pulmonary embolism due to falling off of the emboli from deep venous thrombosis. The process of implantation and retrieval is relatively simple and easy. (authors)

  6. Experimental models of developmental hypothyroidism.

    Science.gov (United States)

    Argumedo, G S; Sanz, C R; Olguín, H J

    2012-02-01

    Hypothyroidism is a systemic disease resulting from either thyroid gland's anatomical and functional absence or lack of hypophyseal stimulation, both of which can lead to deficiency in thyroid hormone (TH) production. TH is essential for human and animal development, growth, and function of multiple organs. Children with deficient TH can develop alterations in central nervous system (CNS), striated muscle, bone tissue, liver, bone marrow, and cardiorespiratory system. Among the clinical outlook are signs like breathing difficulty, cardiac insufficiency, dysphagia, and repeated bronchial aspiration, constipation, muscle weakness, cognitive alterations, cochlear dysfunction, reduced height, defects in temperature regulation, anaemia, jaundice, susceptibility to infection, and others. Experimental and clinical studies have shown that TH is very essential for normal brain development. Other research work based on mice pointed out that a reduced level of TH in pregnant mother leads to congenital hypothyroidism in animal models and it is associated with mental retardation, deep neurologic deficiency that impacts on cognitive, learning, and memory functions. The principal experimental model studies that have focused on hypothyroidism are reviewed in this study. This is important on considering the fact that almost all animal species require thyroid hormones for their metabolism. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Transcutaneous Intraluminal Impedance Measurement for Minimally Invasive Monitoring of Gastric Motility: Validation in Acute Canine Models

    Directory of Open Access Journals (Sweden)

    Michael D. Poscente

    2014-01-01

    Full Text Available Transcutaneous intraluminal impedance measurement (TIIM is a new method to cutaneously measure gastric contractions by assessing the attenuation dynamics of a small oscillating voltage emitted by a battery-powered ingestible capsule retained in the stomach. In the present study, we investigated whether TIIM can reliably assess gastric motility in acute canine models. Methods. Eight mongrel dogs were randomly divided into 2 groups: half received an active TIIM pill and half received an identically sized sham capsule. After 24-hour fasting and transoral administration of the pill (active or sham, two force transducers (FT were sutured onto the antral serosa at laparotomy. After closure, three standard cutaneous electrodes were placed on the abdomen, registering the transluminally emitted voltage. Thirty-minute baseline recordings were followed by pharmacological induction of gastric contractions using neostigmine IV and another 30-minute recording. Normalized one-minute baseline and post-neostigmine gastric motility indices (GMIs were calculated and Pearson correlation coefficients (PCCs between cutaneous and FT GMIs were obtained. Statistically significant GMI PCCs were seen in both baseline and post-neostigmine states. There were no significant GMI PCCs in the sham capsule test. Further chronic animal studies of this novel long-term gastric motility measurement technique are needed before testing it on humans.

  8. Rapid development of cardiac dysfunction in a canine model of insulin resistance and moderate obesity.

    Science.gov (United States)

    Broussard, Josiane L; Nelson, Michael D; Kolka, Cathryn M; Bediako, Isaac Asare; Paszkiewicz, Rebecca L; Smith, Laura; Szczepaniak, Edward W; Stefanovski, Darko; Szczepaniak, Lidia S; Bergman, Richard N

    2016-01-01

    The worldwide incidence of obesity and diabetes continues to rise at an alarming rate. A major cause of the morbidity and mortality associated with obesity and diabetes is heart disease, yet the mechanisms that lead to cardiovascular complications remain unclear. We performed cardiac MRI to assess left ventricular morphology and function during the development of moderate obesity and insulin resistance in a well-established canine model (n = 26). To assess the influence of dietary fat composition, we randomised animals to a traditional lard diet (rich in saturated and monounsaturated fat; n = 12), a salmon oil diet (rich in polyunsaturated fat; n = 8) or a control diet (n = 6). High-fat feeding with lard increased body weight and fasting insulin and markedly reduced insulin sensitivity. Lard feeding also significantly reduced left ventricular function, evidenced by a worsening of circumferential strain and impairment in left ventricular torsion. High-fat feeding with salmon oil increased body weight; however, salmon oil feeding did not impair insulin sensitivity or cardiac function. These data emphasise the importance of dietary fat composition on both metabolic and cardiac function, and have important implications for the relationship between diet and health.

  9. Coralline hydroxyapatite bone graft substitutes in a canine metaphyseal defect model: Radiographic-biomechanical correlation

    International Nuclear Information System (INIS)

    Sartoris, D.J.; Resnick, D.; Holmes, R.E.; Tencer, A.F.; Texas Univ., Dallas; Mooney, V.

    1986-01-01

    Radiographic and biomechanical assessment of a new type of bone graft substitute derived from reef-building sea coral was performed in a canine metaphyseal defect model. Blocks of this material and autogenous iliac crest graft were implanted, respectively, into the right and left proximal tibial metaphyses of eight dogs. Qualitative and quantitative radiographic evaluation was performed in the immediate postoperative period and at 6 months after surgery. Biomechanical testing was carried out on all grafts following harvest at 6 months, as well as on nonimplanted coralline hydroxyapatite and autogenous iliac cancellous bone. In contrast to autografts, incorporation of coralline implants was characterized by predictable osseous growth and apposition with preservation of intrinsic architecture. Greater percent increase in radiography density, higher ultimate compressive strength, and lower stiffness with incorporation were documented advantages of coralline hydroxyapatite over autogenous graft. Densitometric measurements correlated moderately with strength for both types of graft material (r=0.65). These promising results have important implications to the clinical application of coralline hydroxyapatite bone graft substitutes as an alternative to autogenous grafting. (orig.)

  10. Evaluation of Osseous Integration of PVD-Silver-Coated Hip Prostheses in a Canine Model

    Directory of Open Access Journals (Sweden)

    Gregor Hauschild

    2015-01-01

    Full Text Available Infection associated with biomaterials used for orthopedic prostheses remains a serious complication in orthopedics, especially tumor surgery. Silver-coating of orthopedic (megaprostheses proved its efficiency in reducing infections but has been limited to surface areas exposed to soft tissues due to concerns of silver inhibiting osseous integration of cementless stems. To close this gap in the bactericidal capacity of silver-coated orthopedic prostheses extension of the silver-coating on surface areas intended for osseous integration seems to be inevitable. Our study reports about a PVD- (physical-vapor-deposition- silver-coated cementless stem in a canine model for the first time and showed osseous integration of a silver-coated titanium surface in vivo. Radiological, histological, and biomechanical analysis revealed a stable osseous integration of four of nine stems implanted. Silver trace elemental concentrations in serum did not exceed 1.82 parts per billion (ppb and can be considered as nontoxic. Changes in liver and kidney functions associated with the silver-coating could be excluded by blood chemistry analysis. This was in accordance with very limited metal displacement from coated surfaces observed by laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS 12 months after implantation. In conclusion our results represent a step towards complete bactericidal silver-coating of orthopedic prostheses.

  11. Metabolism of model organic pollutants in canine respiratory tract mucosa slices

    International Nuclear Information System (INIS)

    Thornton-Manning, J.R.; Gerde, P.; Chen, S.T.; Dahl, A.R.

    1994-01-01

    The high incidence of human bronchial tumors has been correlated with the high fractional deposition of inhaled particles in the bronchi. Polycyclic aromatic hydrocarbons (PAHs) are frequently bound to airborne particles due to their low vapor pressures. It is thought that tumorigenicity may result from the release and subsequent bioactivation of these particle-associated organic compounds in the respiratory tract. Previous studies at ITRI examined the clearance of organic toxicants from various regions of the canine respiratory tract. Their results indicated that, while clearance of a highly lipophilic PAH such as benzo(a)pyrene (BaP) from the thin alveolar epithelium took only a few minutes, clearance through the thicker epithelium of the conducting airways took hours. Slower, diffusion-limited clearance results in higher concentrations of lipophilic compounds in the epithelium of the bronchi. Hence, the ability of these tissues to metabolize organic compounds to water-soluble metabolites or reactive intermediates may be extremely important in their clearance from the respiratory tract and the potential susceptibility of this region of the respiratory tract to cancer. The purpose of the present study was to evaluate the ability of bronchial mucosa to metabolize a model organic pulmonary carcinogen, BaP, to reactive and nonreactive metabolites and to evaluate the diffusion of the parent compound and metabolites through the bronchial mucosa

  12. Evaluation of osseous integration of PVD-silver-coated hip prostheses in a canine model.

    Science.gov (United States)

    Hauschild, Gregor; Hardes, Jendrik; Gosheger, Georg; Stoeppeler, Sandra; Ahrens, Helmut; Blaske, Franziska; Wehe, Christoph; Karst, Uwe; Höll, Steffen

    2015-01-01

    Infection associated with biomaterials used for orthopedic prostheses remains a serious complication in orthopedics, especially tumor surgery. Silver-coating of orthopedic (mega)prostheses proved its efficiency in reducing infections but has been limited to surface areas exposed to soft tissues due to concerns of silver inhibiting osseous integration of cementless stems. To close this gap in the bactericidal capacity of silver-coated orthopedic prostheses extension of the silver-coating on surface areas intended for osseous integration seems to be inevitable. Our study reports about a PVD- (physical-vapor-deposition-) silver-coated cementless stem in a canine model for the first time and showed osseous integration of a silver-coated titanium surface in vivo. Radiological, histological, and biomechanical analysis revealed a stable osseous integration of four of nine stems implanted. Silver trace elemental concentrations in serum did not exceed 1.82 parts per billion (ppb) and can be considered as nontoxic. Changes in liver and kidney functions associated with the silver-coating could be excluded by blood chemistry analysis. This was in accordance with very limited metal displacement from coated surfaces observed by laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) 12 months after implantation. In conclusion our results represent a step towards complete bactericidal silver-coating of orthopedic prostheses.

  13. An evaluation of the histological effects of intra-articular methadone in the canine model.

    Science.gov (United States)

    Jones, Timothy A; Hand, Walter R; Ports, Michael D; Unger, Daniel V; Herbert, Daniel; Pellegrini, Joseph E

    2003-02-01

    Methadone hydrochloride is an opiate that has pharmacodynamic and pharmacokinetic properties that suggest it may provide longer analgesia than morphine when administered via the intra-articular route. However, no studies to date have been conducted examining the effects of intra-articular methadone hydrochloride on local tissues. Therefore, the purpose of this study was to determine the histopathologic effects of intra-articular methadone hydrochloride on local tissues in the canine knee. Nine canines, 1 to 4 years old, weighing between 20 kg and 23 kg were used. All canines had their knees randomized to receive either bupivacaine, 0.5% with epinephrine 1:200,000 (4.5 mL), and 5 mg methadone hydrochloride (0.5 mL) for the study knee, or bupivacaine, 0.5% with epinephrine 1:200,000 (4.5 mL), and 0.5 mL normal saline for the control knee. Serum methadone hydrochloride levels were obtained on all canines at 6 and 24 hours. Canines were randomly assigned to 1 of 3 groups to be euthanized at either 24 hours, 14 days, or 28 days. Following euthanization and necropsy, synovial fluid levels and tissue samples were obtained and examined for histopathologic changes. Synovial fluid samples noted a few white blood cells at 24 hours and none at 14 and 28 days. Tissue samples showed no histopathologic changes, and serum concentration levels of methadone hydrochloride were negligible.

  14. Dual-energy CT based vascular iodine analysis improves sensitivity for peripheral pulmonary artery thrombus detection: An experimental study in canines

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chun Xiang [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Zhang, Long Jiang, E-mail: kevinzhlj@163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Han, Zong Hong; Zhou, Chang Sheng [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Krazinski, Aleksander W.; Silverman, Justin R. [Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Schoepf, U. Joseph [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Lu, Guang Ming, E-mail: cjr.luguangming@vip.163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China)

    2013-12-01

    Purpose: To evaluate the performance of dual-energy CT (DECT) based vascular iodine analysis for the detection of acute peripheral pulmonary thrombus (PE) in a canine model with histopathological findings as the reference standard. Materials and methods: The study protocol was approved by our institutional animal committee. Thrombi (n = 12) or saline (n = 4) were intravenously injected via right femoral vein in sixteen dogs, respectively. CT pulmonary angiography (CTPA) in DECT mode was performed and conventional CTPA images and DECT based vascular iodine studies using Lung Vessels application were reconstructed. Two radiologists visually evaluated the number and location of PEs using conventional CTPA and DECT series on a per-animal and a per-clot basis. Detailed histopathological examination of lung specimens and catheter angiography served as reference standard. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of DECT and CTPA were calculated on a segmental and subsegmental or more distal pulmonary artery basis. Weighted κ values were computed to evaluate inter-modality and inter-reader agreement. Results: Thirteen dogs were enrolled for final image analysis (experimental group = 9, control group = 4). Histopathological results revealed 237 emboli in 45 lung lobes in 9 experimental dogs, 11 emboli in segmental pulmonary arteries, 49 in subsegmental pulmonary arteries, 177 in fifth-order or more distal pulmonary arteries. Overall sensitivity, specificity, accuracy, PPV, and NPV for CTPA plus DECT were 93.1%, 76.9%, 87.8%, 89.4%, and 84.2% for the detection of pulmonary emboli. With CTPA versus DECT, sensitivities, specificities, accuracies, PPVs, and NPVs are all 100% for the detection of pulmonary emboli on a segmental pulmonary artery basis, 88.9%, 100%, 96.0%, 100%, and 94.1% for CTPA and 90.4%, 93.0%, 92.0%, 88.7%, and 94.1% for DECT on a subsegmental pulmonary artery basis; 23.8%, 96.4%, 50.4%, 93

  15. Anti-tumour efficacy of etoposide alone and in combination with piroxicam against canine osteosarcoma in a xenograft model.

    Science.gov (United States)

    Ong, S M; Saeki, K; Kok, M K; Tanaka, Y; Choisunirachon, N; Yoshitake, R; Nishimura, R; Nakagawa, T

    2017-08-01

    Osteosarcoma (OSA) in dogs is locally invasive and highly malignant. Distant metastasis is the most common cause of death. To date, the survival rate in dogs with OSA remains poor. The cytotoxic effects of etoposide against canine OSA cell lines, either alone or in combination with piroxicam, have been previously demonstrated in vitro. The aim of this study was to evaluate the anti-tumour effect of etoposide alone and in combination with piroxicam on canine OSA using murine models. Etoposide single agent treatment significantly delayed tumour progression with a marked reduction in Ki-67 immunoreactivity in tumour tissue. Concomitant treatment with piroxicam did not enhance the anti-tumour efficacy of etoposide. Etoposide single agent treatment and combination treatment with piroxicam down-regulated survivin expression, but was not followed by increased apoptotic activity. These findings indicate that etoposide might be a promising novel therapeutic for canine OSA. Further investigations into its potential for clinical application in veterinary oncology are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Plasminogen activator inhibitor-1 suppresses endogenous fibrinolysis in a canine model of pulmonary embolism

    International Nuclear Information System (INIS)

    Reilly, C.F.; Fujita, T.; Hutzelmann, J.E.; Mayer, E.J.; Shebuski, R.J.

    1991-01-01

    Plasminogen activator inhibitor-1 (PAI-1), the specific, fast-acting inhibitor of tissue-type plasminogen activator (t-PA), binds to fibrin and has been found in high concentrations within arterial thrombi. These findings suggest that the localization of PAI-1 to a thrombus protects that same thrombus from fibrinolysis. In this study, clot-bound PAI-1 was assessed for its ability to suppress clot lysis in vivo. Autologous, canine whole blood clots were formed in the presence of increasing amounts of activated PAI-1 (0-30 micrograms/ml). Approximately 6-8% of the PAI-1 bound to the clots under the experimental conditions. Control and PAI-1-enriched clots containing iodine-125-labeled fibrin (ogen) were homogenized, washed to remove nonbound elements, and delivered to the lungs of anesthetized dogs where the homogenates subsequently underwent lysis by the endogeneous fibrinolytic system. 125I-labeled fibrin degradation products appeared in the blood of control animals within 10 minutes and were maximal by 90 minutes. PAI-1 reduced fibrin degradation product release in a dose-responsive manner at all times between 30 minutes and 5 hours (greater than or equal to 76% inhibition at 30 minutes, PAI-1 greater than or equal to 6 micrograms/ml). PAI-1 also suppressed D-dimer release from clots containing small amounts of human fibrin (ogen). t-PA administration attenuated the effects of PAI-1, whereas latent PAI-1 (20 micrograms/ml) had no effect on clot lysis. Blood levels of PA and PAI activity remained unaltered during these experiments. The results indicate that PAI-1 markedly inhibits endogenous fibrinolysis in vivo and, moreover, suggest that the localization of PAI-1 to a forming thrombus is an important physiological mechanism for subsequent thrombus stabilization

  17. Evaluation of helper-dependent canine adenovirus vectors in a 3D human CNS model

    Science.gov (United States)

    Simão, Daniel; Pinto, Catarina; Fernandes, Paulo; Peddie, Christopher J.; Piersanti, Stefania; Collinson, Lucy M.; Salinas, Sara; Saggio, Isabella; Schiavo, Giampietro; Kremer, Eric J.; Brito, Catarina; Alves, Paula M.

    2017-01-01

    Gene therapy is a promising approach with enormous potential for treatment of neurodegenerative disorders. Viral vectors derived from canine adenovirus type 2 (CAV-2) present attractive features for gene delivery strategies in the human brain, by preferentially transducing neurons, are capable of efficient axonal transport to afferent brain structures, have a 30-kb cloning capacity and have low innate and induced immunogenicity in pre-clinical tests. For clinical translation, in-depth pre-clinical evaluation of efficacy and safety in a human setting is primordial. Stem cell-derived human neural cells have a great potential as complementary tools by bridging the gap between animal models, which often diverge considerably from human phenotype, and clinical trials. Herein, we explore helper-dependent CAV-2 (hd-CAV-2) efficacy and safety for gene delivery in a human stem cell-derived 3D neural in vitro model. Assessment of hd-CAV-2 vector efficacy was performed at different multiplicities of infection, by evaluating transgene expression and impact on cell viability, ultrastructural cellular organization and neuronal gene expression. Under optimized conditions, hd-CAV-2 transduction led to stable long-term transgene expression with minimal toxicity. hd-CAV-2 preferentially transduced neurons, while human adenovirus type 5 (HAdV5) showed increased tropism towards glial cells. This work demonstrates, in a physiologically relevant 3D model, that hd-CAV-2 vectors are efficient tools for gene delivery to human neurons, with stable long-term transgene expression and minimal cytotoxicity. PMID:26181626

  18. Canine degenerative myelopathy: biochemical characterization of superoxide dismutase 1 in the first naturally occurring non-human amyotrophic lateral sclerosis model.

    Science.gov (United States)

    Crisp, Matthew J; Beckett, Jeffrey; Coates, Joan R; Miller, Timothy M

    2013-10-01

    Mutations in canine superoxide dismutase 1 (SOD1) have recently been shown to cause canine degenerative myelopathy, a disabling neurodegenerative disorder affecting specific breeds of dogs characterized by progressive motor neuron loss and paralysis until death, or more common, euthanasia. This discovery makes canine degenerative myelopathy the first and only naturally occurring non-human model of amyotrophic lateral sclerosis (ALS), closely paralleling the clinical, pathological, and genetic presentation of its human counterpart, SOD1-mediated familial ALS. To further understand the biochemical role that canine SOD1 plays in this disease and how it may be similar to human SOD1, we characterized the only two SOD1 mutations described in affected dogs to date, E40K and T18S. We show that a detergent-insoluble species of mutant SOD1 is present in spinal cords of affected dogs that increases with disease progression. Our in vitro results indicate that both canine SOD1 mutants form enzymatically active dimers, arguing against a loss of function in affected homozygous animals. Further studies show that these mutants, like most human SOD1 mutants, have an increased propensity to form aggregates in cell culture, with 10-20% of cells possessing visible aggregates. Creation of the E40K mutation in human SOD1 recapitulates the normal enzymatic activity but not the aggregation propensity seen with the canine mutant. Our findings lend strong biochemical support to the toxic role of SOD1 in canine degenerative myelopathy and establish close parallels for the role mutant SOD1 plays in both canine and human disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Experimental models of liver fibrosis.

    Science.gov (United States)

    Yanguas, Sara Crespo; Cogliati, Bruno; Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Leclercq, Isabelle; Vinken, Mathieu

    2016-05-01

    Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research.

  20. Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

    Science.gov (United States)

    Varela, Marta; Hancox, Jules C.; Aslanidi, Oleg V.

    2016-01-01

    Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are

  1. Image-Based Macro-Micro Finite Element Models of a Canine Femur with Implant Design Implications

    Science.gov (United States)

    Ghosh, Somnath; Krishnan, Ganapathi; Dyce, Jonathan

    2006-06-01

    In this paper, a comprehensive model of a bone-cement-implant assembly is developed for a canine cemented femoral prosthesis system. Various steps in this development entail profiling the canine femur contours by computed tomography (CT) scanning, computer aided design (CAD) reconstruction of the canine femur from CT images, CAD modeling of the implant from implant blue prints and CAD modeling of the interface cement. Finite element analysis of the macroscopic assembly is conducted for stress analysis in individual components of the system, accounting for variation in density and material properties in the porous bone material. A sensitivity analysis is conducted with the macroscopic model to investigate the effect of implant design variables on the stress distribution in the assembly. Subsequently, rigorous microstructural analysis of the bone incorporating the morphological intricacies is conducted. Various steps in this development include acquisition of the bone microstructural data from histological serial sectioning, stacking of sections to obtain 3D renderings of void distributions, microstructural characterization and determination of properties and, finally, microstructural stress analysis using a 3D Voronoi cell finite element method. Generation of the simulated microstructure and analysis by the 3D Voronoi cell finite element model provides a new way of modeling complex microstructures and correlating to morphological characteristics. An inverse calculation of the material parameters of bone by combining macroscopic experiments with microstructural characterization and analysis provides a new approach to evaluating properties without having to do experiments at this scale. Finally, the microstructural stresses in the femur are computed using the 3D VCFEM to study the stress distribution at the scale of the bone porosity. Significant difference is observed between the macroscopic stresses and the peak microscopic stresses at different locations.

  2. Establishing an in vivo model of canine prostate carcinoma using the new cell line CT1258

    Directory of Open Access Journals (Sweden)

    Winkler Susanne

    2008-08-01

    Full Text Available Abstract Background Prostate cancer is a frequent finding in man. In dogs, malignant disease of the prostate is also of clinical relevance, although it is a less common diagnosis. Even though there are numerous differences in origin and development of the disease, man and dog share many similarities in the pathological presentation. For this reason, the dog might be a useful animal model for prostate malignancies in man. Although prostate cancer is of great importance in veterinary medicine as well as in comparative medicine, there are only few cell lines available. Thus, it was the aim of the present study to determine whether the formerly established prostate carcinoma cell line CT1258 is a suitable tool for in vivo testing, and to distinguish the growth pattern of the induced tumours. Methods For characterisation of the in vivo behaviour of the in vitro established canine prostate carcinoma cell line CT1258, cells were inoculated in 19 NOD.CB17-PrkdcScid/J (in the following: NOD-Scid mice, either subcutaneously or intraperitoneally. After sacrifice, the obtained specimens were examined histologically and compared to the pattern of the original tumour in the donor. Cytogenetic investigation was performed. Results The cell line CT 1258 not only showed to be highly tumourigenic after subcutaneous as well as intraperitoneal inoculation, but also mimicked the behaviour of the original tumour. Conclusion Tumours induced by inoculation of the cell line CT1258 resemble the situation in naturally occurring prostate carcinoma in the dog, and thus could be used as in vivo model for future studies.

  3. Transcutaneous glomerular filtration rate measurement in a canine animal model of chronic kidney disease.

    Science.gov (United States)

    Mondritzki, Thomas; Steinbach, Sarah M L; Boehme, Philip; Hoffmann, Jessica; Kullmann, Maximilian; Schock-Kusch, Daniel; Vogel, Julia; Kolkhof, Peter; Sandner, Peter; Bischoff, Erwin; Hüser, Jörg; Dinh, Wilfried; Truebel, Hubert

    Quantitative assessment of renal function by measurement of glomerular filtration rate (GFR) is an important part of safety and efficacy evaluation in preclinical drug development. Existing methods are often time consuming, imprecise and associated with animal burden. Here we describe the comparison between GFR determinations with sinistrin (PS-GFR) and fluorescence-labelled sinistrin-application and its transcutaneous detection (TD-GFR) in a large animal model of chronic kidney disease (CKD). TD-GFR measurements compared to a standard method using i.v. sinistrin were performed in a canine model. Animals were treated with one-sided renal wrapping (RW) followed by renal artery occlusion (RO). Biomarker and remote hemodynamic measurements were performed. Plasma sinistrin in comparison to transcutaneous derived GFR data were determined during healthy conditions, after RW and RW+RO. RW alone did not led to any significant changes in renal function, neither with PS-GFR nor TD-GFR. Additional RO showed a rise in blood pressure (+68.0mmHg), plasma urea (+28.8mmol/l), creatinine (+224,4μmol/l) and symmetric dimethylarginine (SDMA™; +12.6μg/dl). Plasma sinistrin derived data confirmed the expected drop (-44.7%, p<0.0001) in GFR. The calculated transcutaneous determined Fluorescein Isothiocyanate (FITC)-sinistrin GFR showed no differences to plasma sinistrin GFR at all times. Both methods were equaly sensitive to diagnose renal dysfunction in the affected animals. Renal function assessment using TD-GFR is a valid method to improve preclinical drug discovery and development. Furthermore, TD-GFR method offers advantages in terms of reduced need for blood sampling and thus decreasing animal burden compared to standard procedures. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Diverse bone morphogenetic protein expression profiles and smad pathway activation in different phenotypes of experimental canine mammary tumors.

    Directory of Open Access Journals (Sweden)

    Helena Wensman

    Full Text Available BACKGROUND: BMPs are currently receiving attention for their role in tumorigenesis and tumor progression. Currently, most BMP expression studies are performed on carcinomas, and not much is known about the situation in sarcomas. METHODOLOGY/PRINCIPAL FINDINGS: We have investigated the BMP expression profiles and Smad activation in clones from different spontaneous canine mammary tumors. Spindle cell tumor and osteosarcoma clones expressed high levels of BMPs, in particular BMP-2, -4 and -6. Clones from a scirrhous carcinoma expressed much lower BMP levels. The various clones formed different tumor types in nude mice but only clones that expressed high levels of BMP-6 gave bone formation. Phosphorylated Smad-1/5, located in the nucleus, was detected in tumors derived from clones expressing high levels of BMPs, indicating an active BMP signaling pathway and BMP-2 stimulation of mammary tumor cell clones in vitro resulted in activation of the Smad-1/5 pathway. In contrast BMP-2 stimulation did not induce phosphorylation of the non-Smad pathway p38 MAPK. Interestingly, an increased level of the BMP-antagonist chordin-like 1 was detected after BMP stimulation of non-bone forming clones. CONCLUSIONS/SIGNIFICANCE: We conclude that the specific BMP expression repertoire differs substantially between different types of mammary tumors and that BMP-6 expression most probably has a biological role in bone formation of canine mammary tumors.

  5. MRI-based quantification of Duchenne muscular dystrophy in a canine model

    Science.gov (United States)

    Wang, Jiahui; Fan, Zheng; Kornegay, Joe N.; Styner, Martin A.

    2011-03-01

    Duchenne muscular dystrophy (DMD) is a progressive and fatal X-linked disease caused by mutations in the DMD gene. Magnetic resonance imaging (MRI) has shown potential to provide non-invasive and objective biomarkers for monitoring disease progression and therapeutic effect in DMD. In this paper, we propose a semi-automated scheme to quantify MRI features of golden retriever muscular dystrophy (GRMD), a canine model of DMD. Our method was applied to a natural history data set and a hydrodynamic limb perfusion data set. The scheme is composed of three modules: pre-processing, muscle segmentation, and feature analysis. The pre-processing module includes: calculation of T2 maps, spatial registration of T2 weighted (T2WI) images, T2 weighted fat suppressed (T2FS) images, and T2 maps, and intensity calibration of T2WI and T2FS images. We then manually segment six pelvic limb muscles. For each of the segmented muscles, we finally automatically measure volume and intensity statistics of the T2FS images and T2 maps. For the natural history study, our results showed that four of six muscles in affected dogs had smaller volumes and all had higher mean intensities in T2 maps as compared to normal dogs. For the perfusion study, the muscle volumes and mean intensities in T2FS were increased in the post-perfusion MRI scans as compared to pre-perfusion MRI scans, as predicted. We conclude that our scheme successfully performs quantitative analysis of muscle MRI features of GRMD.

  6. Determination of selenium status using the nail biologic monitor in a canine model

    International Nuclear Information System (INIS)

    Steven Morris, J.; Spate, V.L.; Ruth Ann Ngwenyama; Waters, D.J.

    2012-01-01

    Toenails and fingernails are routinely used to estimate selenium status in epidemiological studies; however, literature validating nail selenium concentration as a surrogate for critical organs is limited. In this study diets of intact male dogs were selenium supplemented at two physiological levels (3 and 6 μg/kg/day) in two different forms, selenomethionine and selenium-enriched bioformed yeast. The selenium-adequate basal diet consumed by the treatment and control groups during the 4-week run-in period and throughout the trial contained 0.3 ppm selenium. After 7 months the dogs in the two treatment groups and the control group were euthanized. Representative tissue samples from prostate, brain, liver, heart and skeletal muscle were collected, rinsed and frozen. Toenail clippings from multiple toes were also collected. Selenium was determined by neutron activation analysis using Se77m (half life = 17.4 s) at the University of Missouri Research Reactor Center. NIST SRM 1577, Bovine Liver was analyzed as a quality control. The analysts were blinded to control and treatment group assignments. As expected, tissue selenium levels increased proportionally with supplementation. A slightly greater increase in tissue selenium was observed for the purified selenomethionine compared to the bioformed yeast; however this trend was significant only for brain tissue. Toenail selenium concentrations and tissue selenium were highly correlated (p < 0.003) with Pearson coefficients of 0.759 (skeletal muscle), 0.745 (heart), 0.729 (brain), 0.723 (prostate), and 0.632 (liver). The toenail biologic monitor accurately assesses selenium status in skeletal muscle, heart, brain, prostate, and liver in the canine model. (author)

  7. Study on the related factors influencing the formation of intra-aneurysmal thrombosis in the established side-wall aneurysmal model in canine

    International Nuclear Information System (INIS)

    Zhou Bing; Li Minghua; Wang Jianbo; Zhu Yueqi; Yuan Jianhua; Yu Wenqiang

    2011-01-01

    Objective: To analyze the related factors influencing the formation of intra-aneurysmal thrombosis (IAT) in the established side-wall aneurysmal model in canine, and to discuss the measures to prevent the occurrence of IAT. Methods: Twenty canines were randomly divided into 4 groups for building side-wall aneurysmal model: group A, vertical aneurysm without use of postoperative anticoagulation medication; group B, vertical aneurysm with use of postoperative anticoagulation medication; group C, oblique aneurysm without use of postoperative anticoagulation medication; and group D, oblique aneurysm with use of postoperative anticoagulation medication. Angiography was performed to evaluate the IAT. The potential related factors influencing the formation of IAT, including sex, age, operative time, aneurysmal morphology, postoperative anticoagulation medication and cervical hematoma, were statistically analysed with emphasis on aneurysmal morphology and the use of postoperative anticoagulation medication. The statistical software SPSS 12.0 was employed. Results: A total of 40 aneurysms were successfully established in 20 canines. Cervical hematoma occurred in 7 canines and IAT developed in 8 aneurysms. The univariate analysis showed that the formation of IAT was significantly influenced by the aneurysmal morphology and cervical hematoma. Surprisingly, the formation of IAT bore no relation to the postoperative anticoagulation, whether the medication was employed or not, which was further confirmed by stratified analysis. Conclusion: To establish oblique aneurysm and to reduce the occurrence of cervical hematoma can effectively decrease the incidence of IAT in established side-wall aneurysmal model in canine. The postoperative anticoagulation medication can not decrease the incidence of IAT. (authors)

  8. A novel canine model of portal vein stenosis plus thioacetamide administration-induced cirrhotic portal hypertension with hypersplenism.

    Science.gov (United States)

    Lin, Dexin; Wu, Xianbin; Ji, Xiaoke; Zhang, Qiyu; Lin, YuanWei; Chen, WeiJian; Jin, Wangxun; Deng, Liming; Chen, Yunzhi; Chen, Bicheng; Li, Jianmin

    2012-01-01

    Current large animal models that could closely resemble the typical features of cirrhotic portal hypertension in human have not been well established. Thus, we aimed to develop and describe a reliable and reproducible canine cirrhosis model of portal hypertension. A total of 30 mongrel dogs were randomly divided into four groups: 1 (control; n = 5), 2 (portal vein stenosis [PVS]; n = 5], 3 (thioacetamide [TAA]; n = 5), and 4 (PVS plus TAA; n = 15). After 4-months modeling period, liver and spleen CT perfusion, abdominal CT scans, portal hemodynamics, gastroscopy, hepatic function, blood routine, the bone marrow, liver, and spleen histology were studied. The animals in group 2 (PVS) developed extrahepatic portosystemic collateral circulation, particularly esophageal varices, without hepatic cirrhosis and portal hypertension. Animals from group 3 (TAA) presented mild cirrhosis and portal hypertension without significant symptoms of esophageal varices and hypersplenism. In contrast, animals from group 4 (PVS + TAA) showed well-developed micronodular and macronodular cirrhosis, associated with significant portal hypertension and hypersplenism. The combination of PVS and TAA represents a novel, reliable, and reproducible canine cirrhosis model of portal hypertension, which is associated with the typical characteristics of portal hypertension, including hypersplenism.

  9. Studies on diagnosis of lung emphysema by CT image using experimental models and clinical cases

    International Nuclear Information System (INIS)

    Nakatani, Seiki

    1998-01-01

    Since the detailed report between the degree of functional disorder in lung emphysema and the analysis of CT image is quite unknown, the present study was attempted to produce the experimental model of lung emphysema with various stages by the administration of papain to the focal lobe in canine lung. Using this model or clinical lung emphysema, the relationship between the degree of destruction of alveolar walls, clinical pulmonary functions and CT images was investigated. CT scan was performed at the level of 50% vital capacity in both experimental models and clinical subjects by using spirometric gating CT. CT density histogram was obtained from CT image which was produced by using the developed software for this purpose. Densitometric parameters, such as mean CT value, %LAA, the peak in the histogram and 5% tile were selected from CT image. Papain solution of 5 mg/kg body weight was cumulatively administered to the left lower lobe in canine lung, resulting in the destruction of lung alveolar walls in parallel to the increasing dosage of papain. There was a significant correlation between not only the increasing dosage of papain, but also %FEV 1.0 and CT densitometric parameters, indicating that the histological changes of alveolar walls and the lung function in lung emphysema could be estimated by analysis of CT image. These experimental and clinical studies suggest that the analysis of CT image can reflect the pathophysiological changes in the lung and be useful for precise clinical diagnosis of lung emphysema. (author)

  10. Dual AAV Gene Therapy for Duchenne Muscular Dystrophy with a 7-kb Mini-Dystrophin Gene in the Canine Model.

    Science.gov (United States)

    Kodippili, Kasun; Hakim, Chady H; Pan, Xiufang; Yang, Hsiao T; Yue, Yongping; Zhang, Yadong; Shin, Jin-Hong; Yang, N Nora; Duan, Dongsheng

    2018-03-01

    Dual adeno-associated virus (AAV) technology was developed in 2000 to double the packaging capacity of the AAV vector. The proof of principle has been demonstrated in various mouse models. Yet, pivotal evidence is lacking in large animal models of human diseases. Here we report expression of a 7-kb canine ΔH2-R15 mini-dystrophin gene using a pair of dual AAV vectors in the canine model of Duchenne muscular dystrophy (DMD). The ΔH2-R15 minigene is by far the most potent synthetic dystrophin gene engineered for DMD gene therapy. We packaged minigene dual vectors in Y731F tyrosine-modified AAV-9 and delivered to the extensor carpi ulnaris muscle of a 12-month-old affected dog at the dose of 2 × 10 13 viral genome particles/vector/muscle. Widespread mini-dystrophin expression was observed 2 months after gene transfer. The missing dystrophin-associated glycoprotein complex was restored. Treatment also reduced muscle degeneration and fibrosis and improved myofiber size distribution. Importantly, dual AAV therapy greatly protected the muscle from eccentric contraction-induced force loss. Our data provide the first clear evidence that dual AAV therapy can be translated to a diseased large mammal. Further development of dual AAV technology may lead to effective therapies for DMD and many other diseases in human patients.

  11. Effect of plasma-rich in platelet-derived growth factors on peri-implant bone healing: An experimental study in canines

    Science.gov (United States)

    Birang, Reza; Torabi, Alireza; Shahabooei, Mohammad; Rismanchian, Mansour

    2012-01-01

    Background: Tissue engineering principles can be exploited to enhance alveolar and peri-implant bone reconstruction by applying such biological factors as platelet-derived growth factors. The objective of the present study is to investigate the effect of autologous plasma-rich in growth factors (on the healing of peri-implant bone in canine mandible). Materials and Methods: In this prospective experimental animal study, two healthy canines of the Iranian mix breed were selected. Three months after removing their premolar teeth on both sides of the mandible, 12 implants of the Osteo Implant Corporationsystem, 5 mm in diameter and 10 mm in length, were selected to be implanted. Plasma rich in growth factors (PRGF) were applied on six implants while the other six were used as plain implants without the plasma. The implants were installed in osteotomy sites on both sides of the mandible to be removed after 4 weeks with the surrounding bones using a trephine bur. Mesio-distal sections and implant blocks, 50 μ in diameter containing the peri-implant bone, were prepared By basic fuchin toluidine-bluefor histological and histomorphometric evaluation by optical microscope. The data were analyzed using Mann-Whitney Test (PPRGF and control groups had no statistically significant differences (P=0.261, P=0.2) although the parameters showed higher measured values in the PRGF group. However, compared to the control, application of PRGF had significantly increased bone-to-implant contact (P=0.028) Conclusion: Based on the results, it may be concluded that application of PRGF on the surface of implant may enhance bone-to-implant contact. PMID:22363370

  12. Histotripsy of the Prostate for the Treatment of BPH: Chronic Results From a Canine Model

    Science.gov (United States)

    Hall, Timothy L.; Hempel, Chris R.; Lake, Alison M.; Kieran, Kathy; Ives, Kim; Fowlkes, J. Brian; Cain, Charles A.; Roberts, William W.

    2009-04-01

    Histotripsy was evaluated as a non-invasive BPH treatment. The prostates of 21 canine subjects were targeted with one of three histotripsy doses. Prostates were harvested immediately, 7 days, or 28 days after treatment and assessed for changes. Lower treatment doses were found to produced scattered cellular disruption and hemorrhage that was sometimes reversible. Higher doses perforated the urethra and produced cavities in the glandular prostate that healed to leave an enlarged urinary channel.

  13. A predictive model for canine dilated cardiomyopathy-a meta-analysis of Doberman Pinscher data.

    Science.gov (United States)

    Simpson, Siobhan; Edwards, Jennifer; Emes, Richard D; Cobb, Malcolm A; Mongan, Nigel P; Rutland, Catrin S

    2015-01-01

    Dilated cardiomyopathy is a prevalent and often fatal disease in humans and dogs. Indeed dilated cardiomyopathy is the third most common form of cardiac disease in humans, reported to affect approximately 36 individuals per 100,000 individuals. In dogs, dilated cardiomyopathy is the second most common cardiac disease and is most prevalent in the Irish Wolfhound, Doberman Pinscher and Newfoundland breeds. Dilated cardiomyopathy is characterised by ventricular chamber enlargement and systolic dysfunction which often leads to congestive heart failure. Although multiple human loci have been implicated in the pathogenesis of dilated cardiomyopathy, the identified variants are typically associated with rare monogenic forms of dilated cardiomyopathy. The potential for multigenic interactions contributing to human dilated cardiomyopathy remains poorly understood. Consistent with this, several known human dilated cardiomyopathy loci have been excluded as common causes of canine dilated cardiomyopathy, although canine dilated cardiomyopathy resembles the human disease functionally. This suggests additional genetic factors contribute to the dilated cardiomyopathy phenotype.This study represents a meta-analysis of available canine dilated cardiomyopathy genetic datasets with the goal of determining potential multigenic interactions relating the sex chromosome genotype (XX vs. XY) with known dilated cardiomyopathy associated loci on chromosome 5 and the PDK4 gene in the incidence and progression of dilated cardiomyopathy. The results show an interaction between known canine dilated cardiomyopathy loci and an unknown X-linked locus. Our study is the first to test a multigenic contribution to dilated cardiomyopathy and suggest a genetic basis for the known sex-disparity in dilated cardiomyopathy outcomes.

  14. A predictive model for canine dilated cardiomyopathy—a meta-analysis of Doberman Pinscher data

    Directory of Open Access Journals (Sweden)

    Siobhan Simpson

    2015-03-01

    Full Text Available Dilated cardiomyopathy is a prevalent and often fatal disease in humans and dogs. Indeed dilated cardiomyopathy is the third most common form of cardiac disease in humans, reported to affect approximately 36 individuals per 100,000 individuals. In dogs, dilated cardiomyopathy is the second most common cardiac disease and is most prevalent in the Irish Wolfhound, Doberman Pinscher and Newfoundland breeds. Dilated cardiomyopathy is characterised by ventricular chamber enlargement and systolic dysfunction which often leads to congestive heart failure. Although multiple human loci have been implicated in the pathogenesis of dilated cardiomyopathy, the identified variants are typically associated with rare monogenic forms of dilated cardiomyopathy. The potential for multigenic interactions contributing to human dilated cardiomyopathy remains poorly understood. Consistent with this, several known human dilated cardiomyopathy loci have been excluded as common causes of canine dilated cardiomyopathy, although canine dilated cardiomyopathy resembles the human disease functionally. This suggests additional genetic factors contribute to the dilated cardiomyopathy phenotype.This study represents a meta-analysis of available canine dilated cardiomyopathy genetic datasets with the goal of determining potential multigenic interactions relating the sex chromosome genotype (XX vs. XY with known dilated cardiomyopathy associated loci on chromosome 5 and the PDK4 gene in the incidence and progression of dilated cardiomyopathy. The results show an interaction between known canine dilated cardiomyopathy loci and an unknown X-linked locus. Our study is the first to test a multigenic contribution to dilated cardiomyopathy and suggest a genetic basis for the known sex-disparity in dilated cardiomyopathy outcomes.

  15. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

    Directory of Open Access Journals (Sweden)

    Christopher M. Fulkerson

    2017-01-01

    Full Text Available Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  16. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs.

    Science.gov (United States)

    Fulkerson, Christopher M; Dhawan, Deepika; Ratliff, Timothy L; Hahn, Noah M; Knapp, Deborah W

    2017-01-01

    Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  17. Storage and allogeneic transplantation of peripheral nerve using a green tea polyphenol solution in a canine model

    Directory of Open Access Journals (Sweden)

    Noguchi Takashi

    2010-11-01

    Full Text Available Abstract Background In our previous study, allogeneic-transplanted peripheral nerve segments preserved for one month in a polyphenol solution at 4°C could regenerate nerves in rodents demonstrated the same extent of nerve regeneration as isogeneic fresh nerve grafts. The present study investigated whether the same results could be obtained in a canine model. Methods A sciatic nerve was harvested from a male beagle dog, divided into fascicules of Sry and β-actin to investigate whether cells of donor origin remained in the allogeneic nerve segments. FK506 concentration was measured in blood samples taken before the animals were killed. Results The total myelinated axon numbers and amplitudes of the muscle action potentials correlated significantly with the blood FK506 concentration. Few axons were observed in the allogeneic-transplanted nerve segments in the PA0.025 group. PCR showed clear Sry-specific bands in specimens from the PA0.1 and PA0.05 groups but not from the PA0.025 group. Conclusions Successful nerve regeneration was observed in the polyphenol-treated nerve allografts when transplanted in association with a therapeutic dose of FK506. The data indicate that polyphenols can protect nerve tissue from ischemic damage for one month; however, the effects of immune suppression seem insufficient to permit allogeneic transplantation of peripheral nerves in a canine model.

  18. EXPERIMENTAL MEASUREMENT, ANALYSIS AND MODELLING ...

    African Journals Online (AJOL)

    30 juin 2010 ... We obtain a good agreement between the resolution of the nonlinear equation of heat and the results obtained by the experimentation. . Keywords: Emissivity, Température, optimal Linearisation, finite elements. 1. ..... basse température, Rapport de Stage de D.E.A, Université Paris 12 – Val de Marne.

  19. Longitudinal quantification of the gingival crevicular fluid proteome during progression from gingivitis to periodontitis in a canine model.

    Science.gov (United States)

    Davis, Ian J; Jones, Andrew W; Creese, Andrew J; Staunton, Ruth; Atwal, Jujhar; Chapple, Iain L C; Harris, Stephen; Grant, Melissa M

    2016-07-01

    Inflammatory periodontal disease is widespread in dogs. This study evaluated site-specific changes in the canine gingival crevicular fluid (GCF) proteome during longitudinal progression from very mild gingivitis to mild periodontitis. Periodontitis diagnosis in dogs requires general anaesthesia with associated risks and costs; our ultimate aim was to develop a periodontitis diagnostic for application in conscious dogs. The objective of this work was to identify potential biomarkers of periodontal disease progression in dogs. Gingival crevicular fluid was sampled from a total of 10 teeth in eight dogs at three different stages of health/disease and samples prepared for quantitative mass spectrometry (data available via ProteomeXchange; identifier PXD003337). A univariate mixed model analysis determined significantly altered proteins between health states and six were evaluated by ELISA. Four hundred and six proteins were identified with 84 present in all samples. The prevalence of 40 proteins was found to be significantly changed in periodontitis relative to gingivitis. ELISA measurements confirmed that haptoglobin was significantly increased. This study demonstrates for the first time that proteins detected by mass spectrometry have potential to identify novel biomarkers for canine periodontal disease. Further work is required to validate additional biomarkers for a periodontitis diagnostic. © 2016 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.

  20. A Posteriori Comparison of Natural and Surgical Destabilization Models of Canine Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Maxim Moreau

    2013-01-01

    Full Text Available For many years Canis familiaris, the domestic dog, has drawn particular interest as a model of osteoarthritis (OA. Here, we optimized the dog model of experimental OA induced by cranial cruciate ligament sectioning. The usefulness of noninvasive complementary outcome measures, such as gait analysis for the limb function and magnetic resonance imaging for structural changes, was demonstrated in this model. Relationships were established between the functional impairment and the severity of structural changes including the measurement of cartilage thinning. In the dog model of naturally occurring OA, excellent test-retest reliability was denoted for the measurement of the limb function. A criterion to identify clinically meaningful responders to therapy was determined for privately owned dogs undergoing clinical trials. In addition, the recording of accelerometer-based duration of locomotor activity showed strong and complementary agreement with the biomechanical limb function. The translation potential of these models to the human OA condition is underlined. A preclinical testing protocol which combines the dog model of experimental OA induced by cranial cruciate ligament transection and the Dog model of naturally occurring OA offers the opportunity to further investigate the structural and functional benefits of disease-modifying strategies. Ultimately, a better prediction of outcomes for human clinical trials would be brought.

  1. A Posteriori Comparison of Natural and Surgical Destabilization Models of Canine Osteoarthritis

    Science.gov (United States)

    Pelletier, Jean-Pierre; d'Anjou, Marc-André; Blond, Laurent; Pelletier, Johanne-Martel; del Castillo, Jérôme R. E.

    2013-01-01

    For many years Canis familiaris, the domestic dog, has drawn particular interest as a model of osteoarthritis (OA). Here, we optimized the dog model of experimental OA induced by cranial cruciate ligament sectioning. The usefulness of noninvasive complementary outcome measures, such as gait analysis for the limb function and magnetic resonance imaging for structural changes, was demonstrated in this model. Relationships were established between the functional impairment and the severity of structural changes including the measurement of cartilage thinning. In the dog model of naturally occurring OA, excellent test-retest reliability was denoted for the measurement of the limb function. A criterion to identify clinically meaningful responders to therapy was determined for privately owned dogs undergoing clinical trials. In addition, the recording of accelerometer-based duration of locomotor activity showed strong and complementary agreement with the biomechanical limb function. The translation potential of these models to the human OA condition is underlined. A preclinical testing protocol which combines the dog model of experimental OA induced by cranial cruciate ligament transection and the Dog model of naturally occurring OA offers the opportunity to further investigate the structural and functional benefits of disease-modifying strategies. Ultimately, a better prediction of outcomes for human clinical trials would be brought. PMID:24288664

  2. Radiation/hyperthermia in canine hemangiopericytomas: A large animal model for therapeutic response

    International Nuclear Information System (INIS)

    Richardson, R.C.; Anderson, V.L.; Voorhees, W.D. III; Blevins, W.E.; Inskeep, T.K.; Janas, W.; Shupe, R.E.; Babbs, C.F.

    1984-01-01

    X-irradiation followed by microwave induced hyperthermia resulted in a 91% objective response rate in 11 dogs with naturally occurring hemangiopericytomas. The authors used a novel statistical procedure to quantitatively evaluate the clinical behavior of locally invasive, non-metastatic tumors undergoing therapy for control of local disease. Utilizing a small sample size, the procedure demonstrated distribution of the data and classical parametric and non-parametric statistical methods, including setting confidence limits on the population mean and placing tolerance limits on a population percentage. Similarities of canine and human hemangiopericytomas were observed. Application of the statistical methods to human and animal trials were apparent

  3. Biphasic pulses enhance bleomycin efficacy in a spontaneous canine genital tumor model of chemoresistance: Sticker sarcoma

    Directory of Open Access Journals (Sweden)

    Citro Gennaro

    2008-11-01

    Full Text Available Abstract Sticker's sarcoma (also known as transmissible venereal tumor is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT, treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy. Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 μs each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations.

  4. A comparative study between mixed-type tumours from human salivary and canine mammary glands

    International Nuclear Information System (INIS)

    Genelhu, Marisa CLS; Cardoso, Sérgio V; Gobbi, Helenice; Cassali, Geovanni D

    2007-01-01

    In comparative pathology, canine mammary tumours have special interest because of their similarities with human breast cancer. Mixed tumours are uncommon lesions in the human breast, but they are found most frequently in the mammary gland of the female dogs and in the human salivary glands. The aim of the study was to compare clinical, morphological and immunohistochemical features of human salivary and canine mammary gland mixed tumours, in order to evaluate the latter as an experimental model for salivary gland tumours. Ten examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex-pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were evaluated. First, clinical and morphologic aspects of benign and malignant variants were compared between the species. Then, streptavidin-biotin-peroxidase immunohistochemistry was performed to detect the expression of cytokeratins, vimentin, p63 protein, estrogen receptor, β-catenin, and E-cadherin. After standardization, similar age and site distributions were observed in human and canine tumours. Histological similarities were identified in the comparison of the benign lesions as well. Metaplastic carcinomas also resembled general aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation. Additionally, immunohistochemical staining further presented similar antigenic expression between lesions. There are many similar features between human salivary and canine mammary gland mixed tumours. This observation is of great relevance for those interested in the study and management of salivary gland tumours, since canine lesions may constitute useful comparative models for their investigations

  5. Self-expandable covered metallic esophageal stent impregnated with beta-emitting radionuclide: an experimental study in canine esophagus

    International Nuclear Information System (INIS)

    Won, Je Hwan; Lee, Jong Doo; Wang, Hee Jung; Kim, Gui-Eon; Kim, Bong Wan; Yim, Hyunee; Han, Sang Keon; Park, Chan H.; Joh, Chul Woo; Kim, Kyung-Hwa; Park, Kyung Bae; Shin, Kyong-Min

    2002-01-01

    Purpose: A specially designed self-expandable covered metallic stent impregnated with the β-emitting radioisotope 166 Ho ( 166 Ho, energy: 1.85 and 1.76 MeV, T((1)/(2)): 26.8 h) was developed at our institute for the purpose of intraluminal palliative brachytherapy, as well as for treating malignant esophageal stricture and swallowing difficulty. The aim of this study was to evaluate the tissue response to brachytherapy and the safety of the radioactive metallic stent with regard to the normal canine esophagus before clinical application. Methods and Materials: 166 Ho was impregnated into the polyurethane membrane (50 μ thickness) covering the outer surface of a self-expandable metallic stent (diameter, 18 mm; length, 40 mm). Stents with radioactivity 4.0-7.8 mCi (Group A, n=15), 1.0-1.8 mCi (Group B, n 5), and 0.5-0.7 mCi (Group C, n=5) were placed in the esophagi of 25 healthy beagle dogs, and the stents were tightly anchored surgically to prevent migration. The estimated radiation dose calculated by Monte Carlo simulation was 194-383 Gy in Group A, 48-90 Gy in Group B, and 23-32 Gy in Group C. The dogs were killed 8-12 weeks after insertion of the stents, and histologic examinations of the esophageal walls were performed. Results: In Group A, 3 of 15 dogs died of wound infection, so specimens were obtained from only 12 dogs; all 12 cases showed esophageal stricture with mucosal ulceration. Microscopically, severe fibrosis and degeneration of the muscular propria were found in 3 dogs, complete fibrosis of the entire esophageal wall was found in 7 dogs, and esophageal fibrosis with radiation damage within periesophageal soft tissue was found in 2 dogs. However, esophageal perforation did not develop, despite extremely high radiation doses. In Group B, glandular atrophy and submucosal fibrosis were found, but the muscular layer was intact. In Group C, no histologic change was found in 3 dogs, but submucosal inflammation and glandular atrophy with intact mucosa

  6. A Cell Kinetic Model of Granulocytopoiesis Under Radiation Exposure: Extension from Murines to Canines and Humans

    Science.gov (United States)

    Hu, Shaowen; Cucinotta, Francis A.

    2009-01-01

    Space radiation poses significant challenges to space travel, and it is essential to understand the possible adverse effects from space radiation exposure to the radiosensitive organ systems that are important for immediate survival of human, e.g., the hematopoietic system. In this presentation a biomathematical model of granulocytopoiesis is described and used to analyze the blood granulocyte changes seen in the blood of mammalians under continuous and acute radiation exposure. This is one of a set of hematopoietic models that have been successfully utilized to simulate and interpret the experimental data of acute and chronic radiation on rodents. We discuss the underlying implicit regulation mechanism and the biological relevance of the kinetic parameters estimation method. Extension of the model to predictions in dogs and humans systems indicates that the modeling results are consistent with the cumulative experimental and empirical data from various sources. This implies the potential to integrate the models into one united system for monitoring the hematopoietic response of various species under irradiation. Based on the evidence of threshold responses of dogs to extended periods of low daily dose exposures, we discuss the potential health risks of the space traveler under chronic stress of low-dose irradiation and the possibly encountered Solar Particle Events.

  7. Canine stifle joint biomechanics associated with tibial plateau leveling osteotomy predicted by use of a computer model.

    Science.gov (United States)

    Brown, Nathan P; Bertocci, Gina E; Marcellin-Little, Denis J

    2014-07-01

    To evaluate effects of tibial plateau leveling osteotomy (TPLO) on canine stifle joint biomechanics in a cranial cruciate ligament (CrCL)-deficient stifle joint by use of a 3-D computer model simulating the stance phase of gait and to compare biomechanics in TPLO-managed, CrCL-intact, and CrCL-deficient stifle joints. Computer simulations of the pelvic limb of a Golden Retriever. A previously developed computer model of the canine pelvic limb was used to simulate TPLO stabilization to achieve a tibial plateau angle (TPA) of 5° (baseline value) in a CrCL-deficient stifle joint. Sensitivity analysis was conducted for tibial fragment rotation of 13° to -3°. Ligament loads, relative tibial translation, and relative tibial rotation were determined and compared with values for CrCL-intact and CrCL-deficient stifle joints. TPLO with a 5° TPA converted cranial tibial translation to caudal tibial translation and increased loads placed on the remaining stifle joint ligaments, compared with results for a CrCL-intact stifle joint. Lateral collateral ligament load was similar, medial collateral ligament load increased, and caudal cruciate ligament load decreased after TPLO, compared with loads for a CrCL-deficient stifle joint. Relative tibial rotation after TPLO was similar to that of a CrCL-deficient stifle joint. Stifle joint biomechanics were affected by TPLO fragment rotation. In the model, stifle joint biomechanics were partially improved after TPLO, compared with CrCL-deficient stifle joint biomechanics, but TPLO did not fully restore CrCL-intact stifle joint biomechanics. Overrotation of the tibial fragment negatively influenced stifle joint biomechanics by increasing caudal tibial translation.

  8. The effect of experimental gastric dilatation-volvulus on adenosine triphosphate content and conductance of the canine gastric and jejunal mucosa.

    Science.gov (United States)

    Peycke, Laura E; Hosgood, Giselle; Davidson, Jacqueline R; Tetens, Joanne; Taylor, H Wayne

    2005-07-01

    The objective of this study was to determine if experimental gastric dilatation volvulus (GDV) would decrease adenosine triphosphate (ATP) concentration and increase membrane conductance of the canine gastric and jejunal mucosa. Male dogs (n = 15) weighing between 20 and 30 kg were used. Dogs were randomly assigned to 1 of 3 equal groups: Group 1 was control, group 2 was GDV, and group 3 was ischemia. All dogs were anesthetized for 210 min. Group 1 had no manipulation. Group 2 had GDV experimentally induced for 120 min followed by decompression, derotation, and reperfusion for 90 min. Group 3 had GDV experimentally induced for 210 min. Gastric (fundus and pylorus) and jejunal tissue was taken at 0, 120, and 210 min from all of the dogs. Tissue was analyzed for ATP concentration, mucosal conductance, and microscopic changes. The ATP concentration in the fundus did not change significantly from baseline in group 2, but decreased significantly below baseline at 210 min in group 3. The ATP concentration in the jejunum decreased significantly below baseline in groups 2 and 3 at 120 min, remaining significantly decreased in group 3 but returning to baseline at 210 min in group 2. Mucosal conductance of the fundus did not change significantly in any dog. Mucosal conductance of the jejunum increased at 120 min in groups 2 and 3, and became significantly increased above baseline at 210 min. The jejunal mucosa showed more profound cellular changes than the gastric mucosa. The jejunum showed substantial decreases in ATP concentration with an increase in mucosal conductance, suggesting cell membrane dysfunction. Dogs sustaining a GDV are likely to have a change in the activity of mucosal cells in the jejunum, which may be important in the pathophysiology of GDV.

  9. Experimental oral immunization of ferret badgers (Melogale moschata) with a recombinant canine adenovirus vaccine CAV-2-E3Δ-RGP and an attenuated rabies virus SRV9.

    Science.gov (United States)

    Zhao, Jinghui; Liu, Ye; Zhang, Shoufeng; Fang, Lijun; Zhang, Fei; Hu, Rongliang

    2014-04-01

    Ferret badgers (Melogale moschata) are a major reservoir of rabies virus in southeastern China. Oral immunization has been shown to be a practical method for wildlife rabies management in Europe and North America. Two groups of 20 ferret badgers were given a single oral dose of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Δ-RGP, or an experimental attenuated rabies virus vaccine, SRV9. At 21 days, all ferret badgers had seroconverted, with serum virus-neutralizing antibodies ranging from 0.1 to 4.5 IU/mL. Titers were >0.50 IU/mL (an acceptable level) in 17/20 and 16/20 animals receiving CAV-2-E3Δ-RGP or SRV9, respectively. The serologic results indicate that the recombinant CAV-2-E3Δ-RGP is at least as effective as the attenuated rabies virus vaccine. Both may be considered for additional research as oral rabies vaccine candidates for ferret badgers.

  10. No evidence of horizontal infection in horses kept in close contact with dogs experimentally infected with canine influenza A virus (H3N8

    Directory of Open Access Journals (Sweden)

    Yamanaka Takashi

    2012-04-01

    Full Text Available Abstract Background Since equine influenza A virus (H3N8 was transmitted to dogs in the United States in 2004, the causative virus, which is called canine influenza A virus (CIV, has become widespread in dogs. To date, it has remained unclear whether or not CIV-infected dogs could transmit CIV to horses. To address this, we tested whether or not close contact between horses and dogs experimentally infected with CIV would result in its interspecies transmission. Methods Three pairs of animals consisting of a dog inoculated with CIV (108.3 egg infectious dose50/dog and a healthy horse were kept together in individual stalls for 15 consecutive days. During the study, all the dogs and horses were clinically observed. Virus titres in nasal swab extracts and serological responses were also evaluated. In addition, all the animals were subjected to a gross pathological examination after euthanasia. Results All three dogs inoculated with CIV exhibited clinical signs including, pyrexia, cough, nasal discharge, virus shedding and seroconversion. Gross pathology revealed lung consolidations in all the dogs, and Streptococcus equi subsp. zooepidemicus was isolated from the lesions. Meanwhile, none of the paired horses showed any clinical signs, virus shedding or seroconversion. Moreover, gross pathology revealed no lesions in the respiratory tracts including the lungs of the horses. Conclusions These findings may indicate that a single dog infected with CIV is not sufficient to constitute a source of CIV infection in horses.

  11. Developing Phenomena Models from Experimental Data

    DEFF Research Database (Denmark)

    Kristensen, Niels Rode; Madsen, Henrik; Jørgensen, Sten Bay

    2003-01-01

    A systematic approach for developing phenomena models from experimental data is presented. The approach is based on integrated application of stochastic differential equation (SDE) modelling and multivariate nonparametric regression, and it is shown how these techniques can be used to uncover...... unknown functionality behind various phenomena in first engineering principles models using experimental data. The proposed modelling approach has significant application potential, e.g. for determining unknown reaction kinetics in both chemical and biological processes. To illustrate the performance...... of the approach, a case study is presented, which shows how an appropriate phenomena model for the growth rate of biomass in a fed-batch bioreactor can be inferred from data....

  12. Developing Phenomena Models from Experimental Data

    DEFF Research Database (Denmark)

    A systematic approach for developing phenomena models from experimental data is presented. The approach is based on integrated application of stochastic differential equation (SDE) modelling and multivariate nonparametric regression, and it is shown how these techniques can be used to uncover...... unknown functionality behind various phenomena in first engineering principles models using experimental data. The proposed modelling approach has significant application potential, e.g. for determining unknown reaction kinetics in both chemical and biological processes. To illustrate the performance...... of the approach, a case study is presented, which shows how an appropriate phenomena model for the growth rate of biomass in a fed-batch bioreactor can be inferred from data....

  13. Adeno-Associated Virus-Mediated Correction of a Canine Model of Glycogen Storage Disease Type Ia

    Science.gov (United States)

    Weinstein, David A.; Correia, Catherine E.; Conlon, Thomas; Specht, Andrew; Verstegen, John; Onclin-Verstegen, Karine; Campbell-Thompson, Martha; Dhaliwal, Gurmeet; Mirian, Layla; Cossette, Holly; Falk, Darin J.; Germain, Sean; Clement, Nathalie; Porvasnik, Stacy; Fiske, Laurie; Struck, Maggie; Ramirez, Harvey E.; Jordan, Juan; Andrutis, Karl; Chou, Janice Y.; Byrne, Barry J.

    2010-01-01

    Abstract Glycogen storage disease type Ia (GSDIa; von Gierke disease; MIM 232200) is caused by a deficiency in glucose-6-phosphatase-α. Patients with GSDIa are unable to maintain glucose homeostasis and suffer from severe hypoglycemia, hepatomegaly, hyperlipidemia, hyperuricemia, and lactic acidosis. The canine model of GSDIa is naturally occurring and recapitulates almost all aspects of the human form of disease. We investigated the potential of recombinant adeno-associated virus (rAAV) vector-based therapy to treat the canine model of GSDIa. After delivery of a therapeutic rAAV2/8 vector to a 1-day-old GSDIa dog, improvement was noted as early as 2 weeks posttreatment. Correction was transient, however, and by 2 months posttreatment the rAAV2/8-treated dog could no longer sustain normal blood glucose levels after 1 hr of fasting. The same animal was then dosed with a therapeutic rAAV2/1 vector delivered via the portal vein. Two months after rAAV2/1 dosing, both blood glucose and lactate levels were normal at 4 hr postfasting. With more prolonged fasting, the dog still maintained near-normal glucose concentrations, but lactate levels were elevated by 9 hr, indicating that partial correction was achieved. Dietary glucose supplementation was discontinued starting 1 month after rAAV2/1 delivery and the dog continues to thrive with minimal laboratory abnormalities at 23 months of age (18 months after rAAV2/1 treatment). These results demonstrate that delivery of rAAV vectors can mediate significant correction of the GSDIa phenotype and that gene transfer may be a promising alternative therapy for this disease and other genetic diseases of the liver. PMID:20163245

  14. Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed trials.

    Directory of Open Access Journals (Sweden)

    Melissa Paoloni

    Full Text Available Molecularly-guided trials (i.e. PMed now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting.A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77% successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days. Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type.Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (<1 week. Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of dogs with cancer into the preclinical

  15. Experimental models of demyelination and remyelination.

    Science.gov (United States)

    Torre-Fuentes, L; Moreno-Jiménez, L; Pytel, V; Matías-Guiu, J A; Gómez-Pinedo, U; Matías-Guiu, J

    2017-08-29

    Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no such specific model able to provide an overview of the disease; multiple models covering the different pathophysiological features of the disease are therefore necessary. We reviewed the different in vitro and in vivo experimental models used in multiple sclerosis research. Concerning in vitro models, we analysed cell cultures and slice models. As for in vivo models, we examined such models of autoimmunity and inflammation as experimental allergic encephalitis in different animals and virus-induced demyelinating diseases. Furthermore, we analysed models of demyelination and remyelination, including chemical lesions caused by cuprizone, lysolecithin, and ethidium bromide; zebrafish; and transgenic models. Experimental models provide a deeper understanding of the different pathogenic mechanisms involved in multiple sclerosis. Choosing one model or another depends on the specific aims of the study. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models.

    Science.gov (United States)

    Sniekers, Yvonne H; Intema, Femke; Lafeber, Floris P J G; van Osch, Gerjo J V M; van Leeuwen, Johannes P T M; Weinans, Harrie; Mastbergen, Simon C

    2008-02-12

    This study evaluates changes in peri-articular bone in two canine models for osteoarthritis: the groove model and the anterior cruciate ligament transection (ACLT) model. Evaluation was performed at 10 and 20 weeks post-surgery and in addition a 3-weeks time point was studied for the groove model. Cartilage was analysed, and architecture of the subchondral plate and trabecular bone of epiphyses was quantified using micro-CT. At 10 and 20 weeks cartilage histology and biochemistry demonstrated characteristic features of osteoarthritis in both models (very mild changes at 3 weeks). The groove model presented osteophytes only at 20 weeks, whereas the ACLT model showed osteophytes already at 10 weeks. Trabecular bone changes in the groove model were small and not consistent. This contrasts the ACLT model in which bone volume fraction was clearly reduced at 10 and 20 weeks (15-20%). However, changes in metaphyseal bone indicate unloading in the ACLT model, not in the groove model. For both models the subchondral plate thickness was strongly reduced (25-40%) and plate porosity was strongly increased (25-85%) at all time points studied. These findings show differential regulation of subchondral trabecular bone in the groove and ACLT model, with mild changes in the groove model and more severe changes in the ACLT model. In the ACLT model, part of these changes may be explained by unloading of the treated leg. In contrast, subchondral plate thinning and increased porosity were very consistent in both models, independent of loading conditions, indicating that this thinning is an early response in the osteoarthritis process.

  17. Gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.

    Directory of Open Access Journals (Sweden)

    Kim M Boerkamp

    Full Text Available BACKGROUND: The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of histiocytic sarcomas. The breed develops two distinct entities of histiocytic neoplasia, a soft tissue form and a visceral form. Gene expression studies of these tumors have value for comparable human diseases such as histiocytic/dendritic cell sarcoma for which knowledge is difficult to accrue due to their rare occurrence. In addition, such studies may help in the search for genetic aberrations underlying the genetic predisposition in this dog breed. METHODS: Microarray analysis and pathway analyses were performed on fresh-frozen tissues obtained from Flatcoated retrievers with localized, soft tissue histiocytic sarcomas (STHS and disseminated, visceral histiocytic sarcomas (VHS and on normal canine spleens from various breeds. Expression differences of nine genes were validated with quantitative real-time PCR (qPCR analyses. RESULTS: QPCR analyses identified the significantly altered expression of nine genes; PPBP, SpiC, VCAM1, ENPEP, ITGAD (down-regulated, and GTSF1, Col3a1, CD90 and LUM (up-regulated in the comparison of both the soft tissue and the visceral form with healthy spleen. DAVID pathway analyses revealed 24 pathways that were significantly involved in the development of HS in general, most of which were involved in the DNA repair and replication process. CONCLUSIONS: This study identified altered expression of nine genes not yet implicated in histiocytic sarcoma manifestations in the dog nor in comparable human histiocytic/dendritic sarcomas. Exploration of the downside effect of canine inbreeding strategies for the study of similar sarcomas in humans might also lead to the identification of genes related to these rare malignancies in the human.

  18. Gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.

    Science.gov (United States)

    Boerkamp, Kim M; van der Kooij, Marieke; van Steenbeek, Frank G; van Wolferen, Monique E; Groot Koerkamp, Marian J A; van Leenen, Dik; Grinwis, Guy C M; Penning, Louis C; Wiemer, Erik A C; Rutteman, Gerard R

    2013-01-01

    The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of histiocytic sarcomas. The breed develops two distinct entities of histiocytic neoplasia, a soft tissue form and a visceral form. Gene expression studies of these tumors have value for comparable human diseases such as histiocytic/dendritic cell sarcoma for which knowledge is difficult to accrue due to their rare occurrence. In addition, such studies may help in the search for genetic aberrations underlying the genetic predisposition in this dog breed. Microarray analysis and pathway analyses were performed on fresh-frozen tissues obtained from Flatcoated retrievers with localized, soft tissue histiocytic sarcomas (STHS) and disseminated, visceral histiocytic sarcomas (VHS) and on normal canine spleens from various breeds. Expression differences of nine genes were validated with quantitative real-time PCR (qPCR) analyses. QPCR analyses identified the significantly altered expression of nine genes; PPBP, SpiC, VCAM1, ENPEP, ITGAD (down-regulated), and GTSF1, Col3a1, CD90 and LUM (up-regulated) in the comparison of both the soft tissue and the visceral form with healthy spleen. DAVID pathway analyses revealed 24 pathways that were significantly involved in the development of HS in general, most of which were involved in the DNA repair and replication process. This study identified altered expression of nine genes not yet implicated in histiocytic sarcoma manifestations in the dog nor in comparable human histiocytic/dendritic sarcomas. Exploration of the downside effect of canine inbreeding strategies for the study of similar sarcomas in humans might also lead to the identification of genes related to these rare malignancies in the human.

  19. Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials.

    Science.gov (United States)

    Paoloni, Melissa; Webb, Craig; Mazcko, Christina; Cherba, David; Hendricks, William; Lana, Susan; Ehrhart, E J; Charles, Brad; Fehling, Heather; Kumar, Leena; Vail, David; Henson, Michael; Childress, Michael; Kitchell, Barbara; Kingsley, Christopher; Kim, Seungchan; Neff, Mark; Davis, Barbara; Khanna, Chand; Trent, Jeffrey

    2014-01-01

    Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting. A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type. Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (strategies may aid cancer drug development.

  20. American Canine Hepatozoonosis

    Science.gov (United States)

    Ewing, S. A.; Panciera, R. J.

    2003-01-01

    American canine hepatozoonosis (ACH) is a tick-borne disease that is spreading in the southeastern and south-central United States. Characterized by marked leukocytosis and periosteal bone proliferation, ACH is very debilitating and often fatal. Dogs acquire infection by ingesting nymphal or adult Gulf Coast ticks (Amblyomma maculatum) that, in a previous life stage, ingested the parasite in a blood meal taken from some vertebrate intermediate host. ACH is caused by the apicomplexan Hepatozoon americanum and has been differentiated from Old World canine hepatozoonosis caused by H. canis. Unlike H. canis, which is transmitted by the ubiquitous brown dog tick (Rhipicephalus sanguineus), H. americanum is essentially an accidental parasite of dogs, for which Gulf Coast ticks are not favored hosts. The geographic portrait of the disease parallels the known distribution of the Gulf Coast tick, which has expanded in recent years. Thus, the endemic cycle of H. americanum involves A. maculatum as definitive host and some vertebrate intermediate host(s) yet to be identified. Although coyotes (Canis latrans) are known to be infected, it is not known how important this host is in maintaining the endemic cycle. This review covers the biology of the parasite and of the tick that transmits it and contrasts ACH with classical canine hepatozoonosis. Clinical aspects of the disease are discussed, including diagnosis and treatment, and puzzling epidemiologic issues are examined. Brief consideration is given to the potential for ACH to be used as a model for study of angiogenesis and of hypertrophic osteoarthropathy. PMID:14557294

  1. Improving the physiological realism of experimental models.

    Science.gov (United States)

    Vinnakota, Kalyan C; Cha, Chae Y; Rorsman, Patrik; Balaban, Robert S; La Gerche, Andre; Wade-Martins, Richard; Beard, Daniel A; Jeneson, Jeroen A L

    2016-04-06

    The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease.

  2. Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Tokihiro, E-mail: toyamamoto@ucdavis.edu [Department of Radiation Oncology, University of California Davis School of Medicine, Sacramento, California 95817 (United States); Kent, Michael S.; Wisner, Erik R. [Department of Surgical and Radiological Sciences, University of California Davis School of Veterinary Medicine, Davis, California 95616 (United States); Johnson, Lynelle R.; Stern, Joshua A. [Department of Medicine and Epidemiology, University of California Davis School of Veterinary Medicine, Davis, California 95616 (United States); Qi, Lihong [Department of Public Health Sciences, University of California Davis, Davis, California 95616 (United States); Fujita, Yukio [Department of Radiation Oncology, Tokai University, Isehara, Kanagawa 259-1193 (Japan); Boone, John M. [Department of Radiology, University of California Davis School of Medicine, Sacramento, California 95817 (United States)

    2016-07-15

    Purpose: Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. Methods: Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t

  3. Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model.

    Science.gov (United States)

    Yamamoto, Tokihiro; Kent, Michael S; Wisner, Erik R; Johnson, Lynelle R; Stern, Joshua A; Qi, Lihong; Fujita, Yukio; Boone, John M

    2016-07-01

    Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t-test. The mean TRE

  4. Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model

    International Nuclear Information System (INIS)

    Yamamoto, Tokihiro; Kent, Michael S.; Wisner, Erik R.; Johnson, Lynelle R.; Stern, Joshua A.; Qi, Lihong; Fujita, Yukio; Boone, John M.

    2016-01-01

    Purpose: Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. Methods: Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t

  5. Hemograma de cães submetidos ao envenenamento experimental por Tityus serrulatus Canine blood profile after experimental envenomation by Tityus serrulatus

    Directory of Open Access Journals (Sweden)

    E.L. Ribeiro

    2009-02-01

    Full Text Available Avaliou-se o hemograma de 12 cães adultos, saudáveis (14,2±5,4kg após a inoculação de veneno do escorpião amarelo (Tityus serrulatus. Os animais foram distribuídos em dois grupos (G, com seis em cada: os do GI foram usados como controle e receberam 0,5mL de salina tamponada com fosfato (PBS por via subcutânea (SC na face medial da coxa esquerda (FMCE, e os do GII receberam veneno liofilizado do T. serrulatus (250µg/kg diluído em PBS por via SC na FMCE. Foram realizadas colheitas de sangue com anticoagulante EDTA a 10% antes da inoculação do veneno (T0 e após 2h, (T1, 6h (T2, 12h (T3, 24h (T4, 48h (T5 e 72h (T6, para contagem de eritrócitos, leucócitos e plaquetas em aparelho contador eletrônico e esfregaços sanguíneos para contagem diferencial de leucócitos. Houve aumento significativo (PThe canine blood profile after scorpion envenomation was evaluated using 12 healthy mongrel male dogs (14.2±5.4kg distributed in two groups, with six animals in each: group I (control group and group II (venom group. The lyophilized yellow scorpion (Tityus serrulatus venom (250µg/kg diluted in 0.5mL phosphate buffered saline (PBS was given to group II animals by subcutaneous injection, in the medial face of the left thigh. Group I animals received only 0.5mL of PBS, by subcutaneous injection, in the medial face of the left thigh. Blood samples were collected with EDTA before (T0 and 2 (T1, 6 (T2, 12 (T3, 24 (T4, 48 (T5, and 72h (T6 after envenomation. Significant increases (P<0.05 in erythrocytes counting, hematocrit and hemoglobin concentration, 2 and 6h after envenomation were observed. Leukocytosis with significant increases (P<0.05 of neutrophils and lymphocytes 2 and 6h after envenomation was found. Then, T. serrulatus venom may induce alterations in blood profile in dogs, probably due to spleen contraction evoked by pain and catecholamines releasing.

  6. Understanding Leadership: An Experimental-Experiential Model

    Science.gov (United States)

    Hole, George T.

    2014-01-01

    Books about leadership are dangerous to readers who fantasize about being leaders or apply leadership ideas as if they were proven formulas. As an antidote, I offer an experimental framework in which any leadership-management model can be tested to gain experiential understanding of the model. As a result one can gain reality-based insights about…

  7. Long-term following-up of viability of spleen autotransplants in the Beagle canine model.

    Science.gov (United States)

    Sajtos, Erika; Balint, Anita; Brath, Endre; Nemeth, Norbert; Peto, Katalin; Kovacs, Judit; Galuska, Laszlo; Varga, Jozsef; Fodor, Zoltan; Furka, Istvan; Miko, Iren

    2012-02-01

    To examine the possible late complications of splenectomy or spleen autotransplantation in large laboratory animal model, in which we need non-invasive or minimal-invasive methods for long-term monitoring of the experimental animals. Experimental groups of beagle dogs were: non-operated control, sham-operated control, splenectomy, spleen autotransplantation with 5 or 10 spleen-chips taken into the greater omentum (Furka's technique). Prior to operations, on the 1(st) postoperative week, monthly till the 6(th) as well as in the 9(th) and 12(th) month, hemorheological examinations were performed. In postoperative 12(th) month colloid scintigraphy and diagnostic laparoscopy were carried out. At the end of the investigation comparative morphological examinations were performed, too. From the 4(th)-5(th) postoperative month filtration function of spleen-autotransplants showed particular restoration compared to splenectomy group. However, the functional results did not reach the values of the control or sham-operated groups. Sham-operated control's scintigraphy nicely showed activity in the spleen. In spleen autotransplantation-groups scintigraphy indicated well the activity of spleen-chips. During diagnostic laparoscopy spleen-chips with their blood supply were found. Histologically, the structure of spleen-autotransplants was similar to normal splenic tissue. The autotransplants are regenerated, their functions have been partly restored, and thus spleen autotransplantation may prevent the possible complications of splenectomy. These parameters and the presented investigative protocol are suitable for long-term following-up of viability of the spleen-autotransplants.

  8. Maxillary growth in a congenital cleft palate canine model for surgical research.

    Science.gov (United States)

    Paradas-Lara, Irene; Casado-Gómez, Inmaculada; Martín, Conchita; Martínez-Sanz, Elena; López-Gordillo, Yamila; González, Pablo; Rodríguez-Bobada, Cruz; Chamorro, Manuel; Arias, Pablo; Maldonado, Estela; Ortega, Ricardo; Berenguer, Beatriz; Martínez-Álvarez, Concepción

    2014-01-01

    We have recently presented the Old Spanish Pointer dog, with a 15-20% spontaneous congenital cleft palate rate, as a unique experimental model of this disease. This study aimed to describe the cleft palate of these dogs for surgical research purposes and to determine whether congenital cleft palate influences maxillofacial growth. Seven newborn Old Spanish Pointer dogs of both sexes, comprising a cleft palate group (n = 4) and a normal palate group (n = 3), were fed using the same technique. Macroscopic photographs and plaster casts from the palate, lateral radiographs and computer tomograms of the skull were taken sequentially over 41 weeks, starting at week 5. The cleft morphology, the size and the tissue characteristics in these dogs resembled the human cleft better than current available animal models. During growth, the cleft width varies. Most of the transverse and longitudinal measures of the palate were statistically lower in the cleft palate group. The cleft palate group showed hypoplasia of the naso-maxillary complex. This model of congenital cleft palate seems suitable for surgical research purposes. A reduced maxillofacial pre- and post-natal development is associated to the congenital cleft palate in the Old Spanish Pointer dog. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  9. Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

    NARCIS (Netherlands)

    Willems, Nicole; Mihov, George; Grinwis, Guy C M; van Dijk, Maarten; Schumann, Detlef; Bos, Clemens; Strijkers, Gustav J; Dhert, Wouter J A; Meij, Björn P; Creemers, Laura B.; Tryfonidou, Marianna A

    Repair of degenerated intervertebral discs (IVD) might be established via intradiscal delivery of biologic therapies. Polyester amide polymers (PEA) were evaluated for in vitro cytotoxicity and in vivo biocompatibility, and thereafter intradiscal application of PEA microspheres (PEAMs) in a canine

  10. Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

    NARCIS (Netherlands)

    Willems, Nicole; Mihov, George; Grinwis, Guy C. M.; van Dijk, Maarten; Schumann, Detlef; Bos, Clemens; Strijkers, Gustav J.; Dhert, Wouter J. A.; Meij, Björn P.; Creemers, Laura B.; Tryfonidou, Marianna A.

    2017-01-01

    Repair of degenerated intervertebral discs (IVD) might be established via intradiscal delivery of biologic therapies. Polyester amide polymers (PEA) were evaluated for in vitro cytotoxicity and in vivo biocompatibility, and thereafter intradiscal application of PEA microspheres (PEAMs) in a canine

  11. EXPERIMENTAL MODEL OF THE PRIMARY MALE HYPOGONADISM

    Directory of Open Access Journals (Sweden)

    P. A. Kulikova

    2014-01-01

    Full Text Available Background: Development of the new methods of treatment of primary male hypogonadism is an urgent medical problem. Its solution requires a suitable experimental model of the disease. Aim: The creation of new experimental model of primary male hypogonadism. Materials and methods: The study was conducted on the male Wistar rats, hypogonadism was modeled by temporary ligation of the distal part of the spermatic cord. Results: It was shown that three-day ligation of the spermatic cord led to persistent disturbance of the testosterone-producing and reproductive functions. These manifestations were reversible at shorter duration of the exposure. Conclusion: The created model of primary male hypogonadism is characterized by the persistent testosterone-producing and reproductive functions disturbance, technical availability, non-toxicity to the other organs and systems. Availability of the model provides new opportunities for the development of approaches to treating diseases of the reproductive organs in men.

  12. Modeling of Experimental Adsorption Isotherm Data

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    Xunjun Chen

    2015-01-01

    Full Text Available Adsorption is considered to be one of the most effective technologies widely used in global environmental protection areas. Modeling of experimental adsorption isotherm data is an essential way for predicting the mechanisms of adsorption, which will lead to an improvement in the area of adsorption science. In this paper, we employed three isotherm models, namely: Langmuir, Freundlich, and Dubinin-Radushkevich to correlate four sets of experimental adsorption isotherm data, which were obtained by batch tests in lab. The linearized and non-linearized isotherm models were compared and discussed. In order to determine the best fit isotherm model, the correlation coefficient (r2 and standard errors (S.E. for each parameter were used to evaluate the data. The modeling results showed that non-linear Langmuir model could fit the data better than others, with relatively higher r2 values and smaller S.E. The linear Langmuir model had the highest value of r2, however, the maximum adsorption capacities estimated from linear Langmuir model were deviated from the experimental data.

  13. Theoretical analysis of alendronate and risedronate effects on canine vertebral remodeling and microdamage

    OpenAIRE

    Wang, Xiang; Erickson, Antonia M.; Allen, Matthew R.; Burr, David B.; Martin, R. Bruce; Hazelwood, Scott J.

    2009-01-01

    Bisphosphonates suppress bone remodeling activity, increase bone volume, and significantly reduce fracture risk in individuals with osteoporosis and other metabolic bone diseases. The objectives of the current study were to develop a mathematical model that simulates control and 1 year experimental results following bisphosphonate treatment (alendronate or risedronate) in the canine fourth lumbar vertebral body, validate the model by comparing simulation predictions to 3 year experimental res...

  14. Constructive remodeling of biologic scaffolds is dependent on early exposure to physiologic bladder filling in a canine partial cystectomy model.

    Science.gov (United States)

    Boruch, Alan V; Nieponice, Alejandro; Qureshi, Irfan R; Gilbert, Thomas W; Badylak, Stephen F

    2010-06-15

    Biologic scaffolds composed of extracellular matrix (ECM) have been used to facilitate the constructive remodeling of several tissue types. Previous studies suggest that the ECM scaffold remodeling process is dependent on microenvironmental factors, including tissue-specific biomechanical loading. The objective of the present study was to evaluate the effects of long-term catheterization (LTC), with its associated inhibition of bladder filling and physiologic biomechanical loading, on ECM scaffold remodeling following partial cystectomy in a canine model. Reconstruction of the partial cystectomy site was performed using ECM scaffolds prepared from porcine small intestinal submucosa (SIS) or porcine urinary bladder matrix (UBM). Animals were randomly assigned to either a long-term catheterization (LTC) group (n=5, catheterized 28 d) or a short-term catheterization group (STC, n=5, catheterized 24 h), and scaffold remodeling was assessed by histologic methods at 4 and 12 wk postoperatively. By 4 wk, animals in the STC group showed a well-developed and highly differentiated urothelium, a robust vascularization network, abundant smooth muscle actin (SMA), and smooth muscle myosin heavy chain (smMHC) expressing spindle-shaped cells, and many neuronal processes associated with newly formed arterioles. In contrast, at 4 wk the scaffolds in LTC animals were not epithelialized, and did not express neuronal markers. The scaffolds in the LTC group developed a dense granulation tissue containing SMA+, smMHC-, spindle-shaped cells that were morphologically and phenotypically consistent with myofibroblasts, but not smooth muscle cells. By 12 wk postoperatively, the ECM scaffolds in the STC animals showed a constructive remodeling response, with a differentiated urothelium and islands of smooth muscle cells within the remodeled scaffold. In contrast, at 12 wk the scaffolds in LTC animals had a remodeling response more consistent with fibrosis even though catheters had been

  15. Hemorrhoids: an experimental model in monkeys

    Directory of Open Access Journals (Sweden)

    Plapler Hélio

    2006-01-01

    Full Text Available PURPOSE: Hemorrhoids are a matter of concern due to a painful outcome. We describe a simple, easy and reliable experimental model to produce hemorrhoids in monkeys. METHODS: 14 monkeys (Cebus apella were used. After general anesthesia, hemorrhoids were induced by ligation of the inferior hemorrhoidal vein, which is very alike to humans. The vein was located through a perianal incision, dissected and ligated with a 3-0 vicryl. The skin was sutured with a 4-0 catgut thread. Animals were kept in appropriate cages and evaluated daily. RESULTS: Nine days later there were hemorrhoidal piles in the anus in fifty percent (50% of the animals. Outcome was unremarkable. There was no bleeding and all animals showed no signs of pain or suffering. CONCLUSION: This is an affordable and reliable experimental model to induce hemorrhoids for experimental studies.

  16. Development of a canine model to enable the preclinical assessment of pH-dependent absorption of test compounds.

    Science.gov (United States)

    Fancher, R Marcus; Zhang, Hongjian; Sleczka, Bogdan; Derbin, George; Rockar, Richard; Marathe, Punit

    2011-07-01

    A preclinical canine model capable of predicting a compound's potential for pH-dependent absorption in humans was developed. This involved the surgical insertion of a gastrostomy feeding tube into the stomach of a beagle dog. The tube was sutured in position to allow frequent withdrawal of gastric fluid for pH measurement. Therefore, it was possible to measure pH in the stomach and assess the effect of gastric pH-modifying agents on the absorption of various test compounds. Fasted gastric pH in the dog showed considerable inter- and intra-animal variability. Pretreatment of pentagastrin (6 µg/kg intramuscularly) 20 min prior to test compound administration was determined to be adequate for simulating fasting stomach pH in humans. Pretreatment with famotidine [40 mg orally] 1 h prior to test compound administration was determined to be adequate for simulating human gastric pH when acid-reducing agents are coadministered. Pentagastrin and famotidine pretreatments were used to test two discovery compounds and distinct differences in their potential for pH-dependent absorption were observed. The model described herein can be used preclinically to screen out compounds, differentiate compounds, and support the assessment of various formulation- and prodrug-based strategies to mitigate the pH effect. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

  17. Cardiac insulin-like growth factor-1 and cyclins gene expression in canine models of ischemic or overpacing cardiomyopathy.

    Science.gov (United States)

    Mahmoudabady, Maryam; Mathieu, Myrielle; Touihri, Karim; Hadad, Ielham; Da Costa, Agnes Mendes; Naeije, Robert; Mc Entee, Kathleen

    2009-10-09

    Insulin-like growth factor-1 (IGF-1), transforming growth factor beta (TGFbeta) and cyclins are thought to play a role in myocardial hypertrophic response to insults. We investigated these signaling pathways in canine models of ischemic or overpacing-induced cardiomyopathy. Echocardiographic recordings and myocardial sampling for measurements of gene expressions of IGF-1, its receptor (IGF-1R), TGFbeta and of cyclins A, B, D1, D2, D3 and E, were obtained in 8 dogs with a healed myocardial infarction, 8 dogs after 7 weeks of overpacing and in 7 healthy control dogs. Ischemic cardiomyopathy was characterized by moderate left ventricular systolic dysfunction and eccentric hypertrophy, with increased expressions of IGF-1, IGF-1R and cyclins B, D1, D3 and E. Tachycardiomyopathy was characterized by severe left ventricular systolic dysfunction and dilation with no identifiable hypertrophic response. In the latter model, only IGF-1 was overexpressed while IGF-1R, cyclins B, D1, D3 and E stayed unchanged as compared to controls. The expressions of TGFbeta, cyclins A and D2 were comparable in the 3 groups. The expression of IGF-1R was correlated with the thickness of the interventricular septum, in systole and diastole, and to cyclins B, D1, D3 and E expression. These results agree with the notion that IGF-1/IGF-1R and cyclins are involved in the hypertrophic response observed in cardiomyopathies.

  18. Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

    Science.gov (United States)

    Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

    2015-01-01

    Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI.

  19. Endoscopic assessment and prediction of prostate urethral disintegration after histotripsy treatment in a canine model.

    Science.gov (United States)

    Schade, George R; Styn, Nicholas R; Hall, Timothy L; Roberts, William W

    2012-02-01

    Histotripsy is a nonthermal focused ultrasound technology that uses acoustic cavitation to homogenize tissue. Previous research has demonstrated that the prostatic urethra is more resistant to histotripsy effects than prostate parenchyma, a finding that may complicate the creation of transurethral resection of the prostate-like treatment cavities. The purpose of this study was to characterize the endoscopic appearance of the prostatic urethra during and after histotripsy treatment and to identify features that are predictive of urethral disintegration. Thirty-five histotripsy treatments were delivered in a transverse plane traversing the prostatic urethra in 17 canine subjects (1-3/prostate ≥1 cm apart). Real-time endoscopy was performed in the first four subjects to characterize development of acute urethral treatment effect (UTE). Serial postprocedure endoscopy was performed in all subjects to assess subsequent evolution of UTE. Endoscopy during histotripsy was feasible with observation of intraurethral cavitation, allowing characterization of the real-time progression of UTE from normal to frank urethral disintegration. While acute urethral fragmentation occurred in 3/35 (8.6%) treatments, frank urethral disintegration developed in 24/35 (68.5%) within 14 days of treatment. Treating until the appearance of hemostatic pale gray shaggy urothelium was the best predictor of achieving urethral fragmentation within 14 days of treatment with positive and negative predictive values of 0.91 and 0.89, respectively. Endoscopic assessment of the urethra may be a useful adjunct to prostatic histotripsy to help guide therapy to ensure urethral disintegration, allowing drainage of the homogenized adenoma and effective tissue debulking.

  20. Optimal Experimental Design for Model Discrimination

    Science.gov (United States)

    Myung, Jay I.; Pitt, Mark A.

    2009-01-01

    Models of a psychological process can be difficult to discriminate experimentally because it is not easy to determine the values of the critical design variables (e.g., presentation schedule, stimulus structure) that will be most informative in differentiating them. Recent developments in sampling-based search methods in statistics make it…

  1. Assessment of metabolic changes in the striatum of a MPTP-intoxicated canine model: in vivo ¹H-MRS study of an animal model for Parkinson's disease.

    Science.gov (United States)

    Choi, Chi-Bong; Kim, Sang-Young; Lee, Sung-Ho; Jahng, Geon-Ho; Kim, Hwi-Yool; Choe, Bo-Young; Ryu, Kyung-Nam; Yang, Dal-Mo; Yim, Sung-Vin; Choi, Woo-Suk

    2011-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta, which projects to the striatum. We induced a selective loss of nigrostriatal dopamine neurons, by infusing the mitochondrial complex 1 inhibitor 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) into adult beagle dogs (N=5). Single voxel ¹H water suppressed magnetic resonance spectroscopy (¹H-MRS) at 3 T was used to assess the metabolic changes in the striatum of canine before and after MPTP intoxication. The metabolite spectra obtained from the striatum (voxel size: 2 cm³) showed a lower N-acetyl aspartate to total creatine (creatine+phosphocreatine) ratio after MPTP intoxication. There were no significant differences in other metabolite ratios such as glutamate+glutamine, choline-containing compounds (glycerophosphocholine+phophorylcholine and myo-inositol). Our findings indicated that ¹H-MRS is a sensitive, noninvasive measure of neural toxicity and biochemical alterations of the striatum in a canine model of PD, and further studies are needed to confirm brain metabolic changes in association with progression of MPTP-intoxication. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Canine thymoma

    International Nuclear Information System (INIS)

    Aronsohn, M.

    1985-01-01

    Thymoma is an uncommon canine neoplasm of thymic epithelial cells. It is seen in various breeds but may occur more frequently in German Shepherd Dogs. Middle-aged or older dogs can be affected and no sex predilection exists. A paraneoplastic syndrome of myasthenia gravis, nonthymic malignant tumors, and/or polymyositis occurs in a significant number of dogs with thymoma. Clinical signs are variable and are related to a space-occupying cranial mediastinal mass and/or manifestations of the paraneo-plastic syndrome. Dyspnea is the most common presenting clinical sign. Thoracic radiographs usually show a cranial mediastinal mass. Lymphoma is the main differential diagnosis. A definitive diagnosis may be made by closed biopsy but is more likely to be confirmed by thoracotomy. Thymomas may be completely contained within the thymic capsule or may spread by local invasion or metastasis. A staging system allows for an accurate prognosis and a therapeutic plan. Surgical removal of encapsulated thymomas may result in long-term survival or cure. Invasive or metastatic thymomas carry a guarded prognosis. Manifestations of the paraneoplastic syndrome complicate treatment. Adjuvant radiation and chemotherapy may be of value for advanced cases; however, adequate clinical trials have not been done in the dog

  3. Preclinical Multimodal Molecular Imaging Using 18F-FDG PET/CT and MRI in a Phase I Study of a Knee Osteoarthritis in In Vivo Canine Model

    Directory of Open Access Journals (Sweden)

    Maria I. Menendez DVM, PhD

    2017-03-01

    Full Text Available The aim of this study was to use a multimodal molecular imaging approach to serially assess regional metabolic changes in the knee in an in vivo anterior cruciate ligament transection (ACLT canine model of osteoarthritis (OA. Five canine underwent ACLT in one knee and the contralateral knee served as uninjured control. Prior, 3, 6, and 12 weeks post-ACLT, the dogs underwent 18F-fluoro-d-glucose (18F-FDG positron emission tomography (PET/computed tomography (CT and magnetic resonance imaging (MRI. The MRI was coregistered with the PET/CT, and 3-dimensional regions of interest (ROIs were traced manually and maximum standardized uptake values (SUVmax were evaluated. 18F-fluoro-d-glucose SUVmax in the ACLT knee ROIs was significantly higher compared to the uninjured contralateral knees at 3, 6, and 12 weeks. Higher 18F-FDG uptake observed in ACLT knees compared to the uninjured knees reflects greater metabolic changes in the injured knees over time. Knee 18F-FDG uptake in an in vivo ACLT canine model using combined PET/CT and MRI demonstrated to be highly sensitive in the detection of metabolic alterations in osseous and nonosteochondral structures comprising the knee joint. 18F-fluoro-d-glucose appeared to be a capable potential imaging biomarker for early human knee OA diagnosis, prognosis, and management.

  4. Macrophages and Uveitis in Experimental Animal Models

    Directory of Open Access Journals (Sweden)

    Salvador Mérida

    2015-01-01

    Full Text Available Resident and infiltrated macrophages play relevant roles in uveitis as effectors of innate immunity and inductors of acquired immunity. They are major effectors of tissue damage in uveitis and are also considered to be potent antigen-presenting cells. In the last few years, experimental animal models of uveitis have enabled us to enhance our understanding of the leading role of macrophages in eye inflammation processes, including macrophage polarization in experimental autoimmune uveoretinitis and the major role of Toll-like receptor 4 in endotoxin-induced uveitis. This improved knowledge should guide advantageous iterative research to establish mechanisms and possible therapeutic targets for human uveitis resolution.

  5. Electrochemical desalination of bricks - Experimental and modeling

    DEFF Research Database (Denmark)

    Skibsted, Gry; Ottosen, Lisbeth M.; Jensen, Pernille Erland

    2015-01-01

    Chlorides, nitrates and sulfates play an important role in the salt-decay of porous materials in buildings and monuments. Electrochemical desalination is a technology able to remove salts from such porous materials in order to stop or prevent the decay. In this paper, experimental and numerical......-contaminated bricks with respect to the monovalent ions is discussed. Comparison between the experimental and the simulation results showed that the proposed numerical model is able to predict electrochemical desalination treatments with remarkable accuracy, and it can be used as a predictive tool...

  6. Irradiation Design for an Experimental Murine Model

    International Nuclear Information System (INIS)

    Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.; Celis, M. A.; Larraga-Gutierrez, J. M.; Garcia-Garduno, O. A.; Rubio-Osornio, M. C.; Custodio-Ramirez, V.; Paz, C.

    2010-01-01

    In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

  7. Study on transcatheter ASD occlusion using modified atrial septal defect occluder with no stainless steel screw in canine model

    International Nuclear Information System (INIS)

    Xuan Bin; Qin Yongwen; Hu Jianqiang; Wu Hong

    2006-01-01

    Objective: To evaluate the safety, biocompatibility and efficacy of transcatheter closure of atrial septal defect (ASD) with no stainless-steel-screw occluder in canine model. Methods: The device was constructed from superelastic Nitinol wires tightly woven into two flat disks and sewed with polyester fibers inside, with a pliable loop on the right-atrial-disk of the device, connecting to the delivery cable. ASD was created by transcatheter puncture and balloon dilatation and then closed by occluder under fluoroscopy in the catheterization laboratory. the location and the influence of the implanted device on function of tricuspid valve and mitral valve were evaluated by echocardiography. At 1, 2, 3 and 6 months after the operation, the animals were killed and autopsy was conducted. Results: Eight dogs with puncture-produced ASD underwent ASD closing procedure successfully. the occluder showed no influence on the function of MV and AV demonstrated by echocardiogram. The two disks of the implanted device were covered with a smooth intact neogenesis layer in all dogs. Endocardial cells fully covered the surface of the two disk without inflammating reaction 3 months later. There was no evidence of corrosion on the surface of the nitinol wire removed from the dog after 6 months. Light microscopic examination of the liver, kidney, lung and spleen showed no evidence of embolization and inflammation. Conclusion: Transcatheter ASD occlusion with new-type occluder is safe, feasible, effective and good biocompatibility with a good prospective clinical application. (authors)

  8. Uptake and distribution of a labeled fatty acid in a canine model of ischemia with and without reperfusion

    International Nuclear Information System (INIS)

    Devous, M.D. Sr.

    1985-01-01

    The relationship between regional myocardial blood flow (RMBF) and the regional distribution of 15-(4-iodophenyl)-9-methyl pentadecanoic acid (9-MPDA) was studied in a canine model of myocardial ischemia with and without reperfusion. Group 1 dogs received 135 min of left anterior descending coronary artery (LAD) occlusion; Group 2 dogs received 90 min of LAD occlusion and 45 min of reflow; and Group 3 dogs received 90 min of LAD occlusion and 3.5 hr of reperfusion. All animals received 9-MPDA 15 min prior to sacrifice, and tracer microspheres prior to occlusion, 5 and 80 min after occlusion, 15 min after reperfusion, and 15 min before the end of reperfusion. In Group 1 (permanent ischemia), 9-MPDA distribution was closely correlated with RMBF both 5 and 80 min after occlusion. In Group 2, 9-MPDA uptake was most closely correlated with reperfusion RMBF rather than ischemic RMBF. However, in 1 animal with good reperfusion, 9-MPDA uptake was reduced and was correlated with ischemic blood flow measured 5 min after occlusion. In Group 3, 9-MPDA uptake was correlated with RMBF measured during the ischemic period and not with reperfusion RMBF. It appears that 9-MPDA uptake is determined by RMBF when flow is limited, or early in reperfusion. With prolonged reperfusion, 9-MPDA uptake is significantly reduced in the ischemic zone in the presence of normal flow. This finding implies that the uptake of this fatty acid during reperfusion is related to myocardial damage (myocardial metabolism?) and not to RMBF

  9. Studies of a novel photosensitizer Pd-bacteriopheophorbide (Tookad) for the prostate cancer PDT in canine model

    Science.gov (United States)

    Huang, Zheng; Chen, Qun; Brun, Pierre-Herve; Wilson, Brian C.; Scherz, Avigdor; Salomon, Yoram; Luck, David L.; Beckers, Jill; Hetzel, Fred W.

    2003-12-01

    Photodynamic therapy (PDT) mediated with vascular acting photosensitizer pd-bacteriopheophorbide (Tookad), is investigated as an alternative modality for the total ablation of prostate cancer. In vivo normal canine prostate is used as the animal model. Interstitial PDT was performed by irradiating the surgically exposed prostates with a diode laser (763 nm, 150 mW/cm) to activate the i.v. infused photosensitizer drug. The effects of two-session PDT were evaluated. The prostate and its adjacent tissues were harvested and subjected to histopathological examination. At one-week, post second-session PDT, the animals recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. Two-session PDT or one single session PDT induced a similar extent of damage. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. Maximum lesion size of over 3 cm in dimension could be achieved with a single 1-cm interstitial treatment, suggesting the therapy is very effective in ablating prostatic tissue. Pharmacokinetic studies show that the photosensitizer is cleared rapidly from the circulation. In conclusion, the novel photosensitizer Tookad mediated PDT may provide an effective alternative to treat prostate cancer.

  10. Tookad-mediated photodynamic effects on the prostate and its adjacent tissues: in vivo study in canine models

    Science.gov (United States)

    Huang, Zheng; Chen, Qun; Luck, David; Beckers, Jill; Blanc, Dominique; Hetzel, Fred W.

    2005-04-01

    Photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (pd-bacteriopheophorbide), was investigated as an alternative treatment modality for prostate cancer. Tookad photodynamic effects on the prostate and its adjacent tissues were evaluated in canine models. Interstitial prostate PDT was performed by irradiating individual lobes with a diode laser (763 nm) and 1-cm cylindrical diffuser fibers at various light doses to activate the IV administered photosensitizer Tookad (1 - 2 mg/kg). The sensitivity of the adjacent tissues to Tookad-PDT was determined by superficially irradiating the surfaces of the bladder, colon, abdominal muscle and pelvic plexus with a microlens fiber at various drug/light doses. PDT effect on the prostatic urethra was evaluated by transurethral irradiation. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathologic examination. At one-week post interstitial prostate PDT, the animals recovered well with little or no urethral complications. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. The bladder, colon, abdominal muscle and pelvic plexus, appeared to also be sensitive to Tookad-PDT at light dose levels greater than 40 Jcm2. Urethral mucosa appeared less sensitive to Tookad-PDT. In conclusion, Tookad-mediated PDT demonstrates very strong vascular effects and can provide an effective alternative for the treatment of localized prostate cancer. Protection of the adjacent tissues should be taken into consideration in the total prostate ablation process due to their sensitivity to the Tookad-mediated PDT.

  11. Development of a urinary lithiasis localizer mechanism to couple ultrasound and extracorporeal lithotripsy equipment in canine model

    Directory of Open Access Journals (Sweden)

    Enrico Andrade

    2006-10-01

    Full Text Available INTRODUCTION: Due to the evolution of extracorporeal lithotripsy equipment (ESWL and presently, the fact that most part of the equipment does not present ultrasound to localize urinary calculi, a system that allows adapting ultrasound equipment to ESWL equipment was developed, disposing only of fluoroscopy. Thus, this equipment was developed and was tested in urinary stones in canine models, to check its precision in relation to fluoroscopy. METHOD: Seven male dogs were utilized with the introduction, in the bladder through the ureteral route, of chalkstones, with initial localization by fluoroscopy, with a further ultrasound coincidence check localization of the vesical stones, being submitted to ESWL with a 3-hour, 21 days and 60 days follow-up after the procedure. RESULTS: Success of localization in all animals was verified presenting elimination of stones in the first micturitions, after ESWL. No complications were verified in those animals for 60 days. CONCLUSION: We verified that this equipment can lead to an update of the equipment that use only fluoroscopy, increasing in this way, their technical capacity in the treatment of urinary calculi, mainly in cases of non-radiopaque stones.

  12. Experimental challenge models for canine leishmaniasis in hamsters and dogs, optimization and application in vaccine research

    NARCIS (Netherlands)

    Poot, Jacqueline

    2006-01-01

    In dogs, leishmaniasis caused by the protozoan parasite Leishmania infantum is a serious and potentially fatal disease. This parasite can also cause zoonotic visceral leishmaniasis in children and immunocompromised adults. A vaccine for dogs would not only be of great value in veterinary medicine

  13. Video-assisted thoracoscopy for diaphragmatic plication: experimental study in a canine model.

    Science.gov (United States)

    Gonzalez-Zamora, Jose F; Perez-Guille, Beatriz; Soriano-Rosales, Rosa E; Jimenez-Bravo-Luna, Miguel A; Gutierrez-Castrellon, Pedro; Ridaura-Sanz, Cecilia; Alvarez, Fernando Villegas

    2005-12-01

    Plication of a nonfunctional hemidiaphragm usually restores altered ventilatory mechanics. This study compared two techniques in performing diaphragmatic plication: video-assisted thoracoscopy (group A) and thoracotomy (group B). Twenty dogs with induced paralysis of the right hemidiaphragm were randomly assigned to one of the two groups. Evaluations were performed before and after plication of the respiratory frequency (f) and lung area (LA) of the affected side. Operative time, time to resumption of walking, ingestion of fluids and solid food, pain intensity, and postoperative complications were measured. Group A had less pain after the surgery (P fluid ingestion (P < 0.05), and earlier resumption of walking (P < 0.019). Four weeks after the procedure, LA was similar in both groups, while a significant decrease in f was recorded in group A (P < 0.02). The remaining evaluated variables showed no differences. Both approaches were effective. Pain recorded in the postoperative period was less and recovery was faster in group A. Complications and surgical times were similar. The video-assisted thoracoscopy is a safe and efficient option for performing diaphragmatic plication in dogs.

  14. Huntington disease: Experimental models and therapeutic perspectives

    International Nuclear Information System (INIS)

    Serrano Sanchez, Teresa; Blanco Lezcano, Lisette; Garcia Minet, Rocio; Alberti Amador, Esteban; Diaz Armesto, Ivan and others

    2011-01-01

    Huntington's disease (HD) is a degenerative dysfunction of hereditary origin. Up to date there is not, an effective treatment to the disease which having lapsed 15 or 20 years advances inexorably, in a slow form, toward the total inability or death. This paper reviews the clinical and morphological characteristics of Huntington's disease as well as the experimental models more commonly used to study this disease, having as source the articles indexed in Medline data base, published in the last 20 years. Advantages and disadvantages of all experimental models to reproduce the disease as well as the perspectives to therapeutic assay have been also considered. the consent of outline reported about the toxic models, those induced by neurotoxins such as quinolinic acid, appears to be the most appropriate to reproduce the neuropathologic characteristic of the disease, an genetic models contributing with more evidence to the knowledge of the disease etiology. Numerous treatments ameliorate clinical manifestations, but none of them has been able to stop or diminish the affectations derived from neuronal loss. At present time it is possible to reproduce, at least partially, the characteristics of the disease in experimentation animals that allow therapy evaluation in HD. from the treatment view point, the more promissory seems to be transplantation of no neuronal cells, taking into account ethical issues and factibility. On the other hand the new technology of interference RNA emerges as a potential therapeutic tool for treatment in HD, and to respond basic questions on the development of the disease.

  15. Histopathologic Evolution of Cardiomyopathy in a Canine Model of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Lygia M.M. Malvestio

    2015-07-01

    Full Text Available Duchenne muscular dystrophy (DMD is a recessive X-linked disorder characterized for mutation in dystrophin gene and manifested by progressive degeneration and necrosis of skeletal and cardiac muscle with replacement leading to generalized muscular weakness and atrophy. The dog Golden Retriever Muscular Dystrophy (GRMD is the best experimental model for DMD, with genotypic and phenotypic manifestations closely of human disease. Similar to patients with DMD, heart failure is a major cause of death in GRMD animals. The objective of this study was to evaluate the pathological progression of myocardial lesions from GRMD dogs in different ages in order to clarify the pathogenesis of Duchenne´s cardiomyopathy. Fragments of left and right ventricle and interventricular septum, from 18 GRMD dogs between 6 to 51 months were collected, fixed, dehydrated, clarified, and finally embedded in paraffin. Five micrometer thick serial sections were obtained and stained with Hematoxylin-Eosin (HE, Picrosirius red, and Von Kossa. Histological analyses were performed at the light microscopy. Myocardial lesions were observed in all GRMD dogs and the sequence of cardiac lesion classified according to according to the age included: abnormal calcium accumulation, myofibrillar necrosis, proliferation of granulation tissue, endomysial and perimysial fibrosis, and finally myocardial fatty infiltration. Interestingly, several Anitschkow cells, the hallmark of rheumatic carditis, were detected in inflammatory infiltrate present at granulation tissue. Our results demonstrate the sequence of cardiac lesions that determine the cardiomyopathy in Golden Retriever dogs affected by DMD and exhibit, for the first time, the Anitschkow cells in the histological findings of this cardiomyopathy. These results are relevant for to clarify the pathogenesis of cardiomyopathy in dogs and humans affected by DMD.

  16. Effects of low-dose cyclophosphamide with piroxicam on tumour neovascularization in a canine oral malignant melanoma-xenografted mouse model.

    Science.gov (United States)

    Choisunirachon, N; Jaroensong, T; Yoshida, K; Saeki, K; Mochizuki, M; Nishimura, R; Sasaki, N; Nakagawa, T

    2015-12-01

    Low-dose cyclophosphamide (CyLD) has shown promise in the treatment of several cancers; however, the effect of CyLD on canine oral malignant melanoma has never been explored. In this study, we investigated the effects of CyLD with or without piroxicam (Px) on tumour neovascularization and vascular normalization in a canine oral malignant melanoma-xenografted mice model. After treatment with CyLD, Px or a combination of both (CyPx), the growth of the tumour in the treatment groups was significantly suppressed compared to the control group at 30 days of treatment. Proliferation index was also significantly reduced by all treatments, only CyPx significantly lowered microvessel density and vascular endothelial growth factor (VEGF) levels. Additionally, CyLD significantly reduced the proportion of normal vessels and caused an imbalance between VEGF and thrombospondin-1. These results suggested that CyPx has potent anti-angiogenic effects in terms of both the number and quality of blood vessels in xenografted canine oral malignant melanoma. © 2013 John Wiley & Sons Ltd.

  17. Adjustment model of thermoluminescence experimental data

    International Nuclear Information System (INIS)

    Moreno y Moreno, A.; Moreno B, A.

    2002-01-01

    This model adjusts the experimental results for thermoluminescence according to the equation: I (T) = I (a i * exp (-1/b i * (T-C i )) where: a i , b i , c i are the i-Th peak adjusted to a gaussian curve. The adjustments of the curve can be operated manual or analytically using the macro function and the solver.xla complement installed previously in the computational system. In this work it is shown: 1. The information of experimental data from a LiF curve obtained from the Physics Institute of UNAM which the data adjustment model is operated in the macro type. 2. A LiF curve of four peaks obtained from Harshaw information simulated in Microsoft Excel, discussed in previous works, as a reference not in macro. (Author)

  18. Comparison of diamond-like carbon-coated nitinol stents with or without polyethylene glycol grafting and uncoated nitinol stents in a canine iliac artery model

    Science.gov (United States)

    Kim, J H; Shin, J H; Shin, D H; Moon, M-W; Park, K; Kim, T-H; Shin, K M; Won, Y H; Han, D K; Lee, K-R

    2011-01-01

    Objective Neointimal hyperplasia is a major complication of endovascular stent placement with consequent in-stent restenosis or occlusion. Improvements in the biocompatibility of stent designs could reduce stent-associated thrombosis and in-stent restenosis. We hypothesised that the use of a diamond-like carbon (DLC)-coated nitinol stent or a polyethylene glycol (PEG)-DLC-coated nitinol stent could reduce the formation of neointimal hyperplasia, thereby improving stent patency with improved biocompatibility. Methods A total of 24 stents were implanted, under general anaesthesia, into the iliac arteries of six dogs (four stents in each dog) using the carotid artery approach. The experimental study dogs were divided into three groups: the uncoated nitinol stent group (n = 8), the DLC-nitinol stent group (n = 8) and the PEG-DLC-nitinol stent group (n = 8). Results The mean percentage of neointimal hyperplasia was significantly less in the DLC-nitinol stent group (26.7±7.6%) than in the nitinol stent group (40.0±20.3%) (p = 0.021). However, the mean percentage of neointimal hyperplasia was significantly greater in the PEG-DLC-nitinol stent group (58.7±24.7%) than in the nitinol stent group (40.0±20.3%) (p = 0.01). Conclusion Our findings indicate that DLC-coated nitinol stents might induce less neointimal hyperplasia than conventional nitinol stents following implantation in a canine iliac artery model; however, the DLC-coated nitinol stent surface when reformed with PEG induces more neointimal hyperplasia than either a conventional or DLC-coated nitinol stent. PMID:21325363

  19. Enhancement of abdominal wall defect repair using allogenic platelet-rich plasma with commercial polyester/cotton fabric (Damour) in a canine model

    Science.gov (United States)

    ABOUELNASR, Khaled; HAMED, Mohamed; LASHEN, Samah; EL-ADL, Mohamed; ELTAYSH, Rasha; TAGAWA, Michihito

    2017-01-01

    Platelet-rich plasma (PRP) has an important role in musculoskeletal surgery; however, it has been underutilized for accelerating the healing of abdominal wall defects in veterinary practice. Therefore, the aim of this study was to evaluate the use of commercial polyester/cotton fabric (Damour) as a new composite mesh for the repair of experimentally induced abdominal wall defects in canine models, and to investigate the possible role of PRP for improving such repair and reducing allied complications. For this purpose, abdominal wall defects were created in 24 healthy mongrel dogs and then repaired with mesh alone (control group) or mesh and allogenic PRP (PRP group). Dogs were euthanized after 2 or 4 months for gross examination of implantation site, detection of adhesion score and hernia recurrence. Moreover, tissue samples were collected for histological and gene expression analyses for neovascularization, collagen formation and tissue incorporation. Hernia recurrence was not recorded in PRP-treated dogs that also displayed significantly more neovascularization and less severe adhesion to the underlings (1.08 ± 0.51) in comparison to control group (2.08 ± 0.99). Histological and molecular evaluation confirmed the gross findings that collagen deposition, new vessel formation, and overexpression of angiogenic and myofibroplastic genes (COL1α1, COL3α1, VEGF and TGFβ1) were observed more frequently in the PRP group, at both time points. In conclusion, we found that addition of allogenic PRP to Damour mesh enhanced neovessel formation, and increased tissue deposition and incorporation, with subsequent reduction of peritoneal adhesion and recurrence rate. PMID:28603214

  20. Evaluation of Partial Transection versus Synovial Debridement of the ACL as Novel Canine Models for Management of ACL Injuries.

    Science.gov (United States)

    Bozynski, Chantelle C; Kuroki, Keiichi; Stannard, James P; Smith, Patrick A; Stoker, Aaron M; Cook, Cristi R; Cook, James L

    2015-10-01

    A major hurdle in investigating important clinical questions in knee ligament treatment is a lack of valid translational animal models. This study characterizes the effects of partial transection versus synovial debridement of the anterior (cranial) cruciate ligament (ACL) in dogs. A total of 27 adult purpose-bred research hounds underwent surgery and were assessed over the following 8 weeks. Dogs were randomized into the following three ACL status groups: sham control (n = 9), intact ACL with synovial debridement (exposed ACL) (n = 9), and partial transection of the ACL (partial tear ACL) (n = 9). Dogs in the exposed ACL group and partial tear ACL group had significantly (p < 0.05) more severe lameness, pain, effusion, reduced function, and reduced comfortable range of motion compared with controls, with the partial tear ACL group being most severely affected. More severe ACL and whole-joint pathology, and radiographic scores for osteoarthritis were present in the partial tear ACL group compared with exposed and/or sham control group. On the basis of these findings, biologic components of ACL injury (exposed ACL) played a role in whole-joint inflammation, but the clinical and pathological effects were more severe when both biologic and biomechanical components were present (i.e., partial tear ACL). These novel canine models were successfully developed to evaluate partial transection versus synovial debridement of the ACL and these models will be used to evaluate treatment options for acute management of ACL injuries. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  1. Ecological niche model of Phlebotomus perniciosus, the main vector of canine leishmaniasis in north-eastern Italy

    Directory of Open Access Journals (Sweden)

    Manuela Signorini

    2014-11-01

    Full Text Available With respect to the epidemiology of leishmaniasis, it is crucial to take into account the ecoclimatic and environ- mental characteristics that influence the distribution patterns of the vector sand fly species. It is also important to consider the possible impact of on-going climate changes on the emergence of this disease. In order to map the potential distribu- tion of Phlebotomus perniciosus, the main vector species of canine leishmaniasis in north-eastern Italy, geographical information systems tools, ecological niche models (ENM and remotely sensed environmental data were applied for a retrospective analysis of an entomological survey conducted in north-eastern Italy over 12 years. Sand fly trapping was conducted from 2001 to 2012 in 175 sites in the provinces of Veneto, Friuli-Venezia Giulia and Trentino-Alto Adige. We developed a predictive model of potential distribution of P. perniciosus using the maximum entropy algorithm software, based on seasonal normalized difference vegetation index, day and night land surface temperature, the Corine land cover 2006, a digital elevation model (GTOPO30 and climate layers obtained from the WorldClim database. The MaxEnt pre- diction found the more suitable habitat for P. perniciosus to be hilly areas (100-300 m above the mean sea level charac- terised by temperate climate during the winter and summer seasons, high winter vegetation cover and moderate rainfall during the activity season of vector sand fly. ENM provided a greater understanding of the geographical distribution and ecological requirements of P. perniciosus in the study area, which can be applied for the development of future surveil- lance strategies.

  2. Characterization of the canine urinary proteome.

    Science.gov (United States)

    Brandt, Laura E; Ehrhart, E J; Scherman, Hataichanok; Olver, Christine S; Bohn, Andrea A; Prenni, Jessica E

    2014-06-01

    Urine is an attractive biofluid for biomarker discovery as it is easy and minimally invasive to obtain. While numerous studies have focused on the characterization of human urine, much less research has focused on canine urine. The objectives of this study were to characterize the universal canine urinary proteome (both soluble and exosomal), to determine the overlap between the canine proteome and a representative human urinary proteome study, to generate a resource for future canine studies, and to determine the suitability of the dog as a large animal model for human diseases. The soluble and exosomal fractions of normal canine urine were characterized using liquid chromatography tandem mass spectrometry (LC-MS/MS). Biological Networks Gene Ontology (BiNGO) software was utilized to assign the canine urinary proteome to respective Gene Ontology categories, such as Cellular Component, Molecular Function, and Biological Process. Over 500 proteins were confidently identified in normal canine urine. Gene Ontology analysis revealed that exosomal proteins were largely derived from an intracellular location, while soluble proteins included both extracellular and membrane proteins. Exosome proteins were assigned to metabolic processes and localization, while soluble proteins were primarily annotated to specific localization processes. Several proteins identified in normal canine urine have previously been identified in human urine where these proteins are related to various extrarenal and renal diseases. The results of this study illustrate the potential of the dog as an animal model for human disease states and provide the framework for future studies of canine renal diseases. © 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.

  3. Experimental tests of proton spin models

    International Nuclear Information System (INIS)

    Ramsey, G.P.; Argonne National Lab., IL

    1989-01-01

    We have developed models for the spin-weighted quark and gluon distribution in a longitudinally polarized proton. The model parameters are determined from current algebra sum rules and polarized deep-inelastic scattering data. A number of different scenarios are presented for the fraction of spin carried the constituent parton distributions. A possible long-range experimental program is suggested for measuring various hard scattering processes using polarized lepton and proton beams. With the knowledge gained from these experiments, we can begin to understand the parton contributions to the proton spin. 28 refs., 5 figs

  4. Experimental In Vivo Models of Candidiasis

    Directory of Open Access Journals (Sweden)

    Esther Segal

    2018-02-01

    Full Text Available Candidiasis is a multifaceted fungal disease including mucosal-cutaneous, visceral, and disseminated infections caused by yeast species of the genus Candida. Candida infections are among the most common human mycoses. Candida species are the third to fourth most common isolates from bloodstream infections in neutropenic or immunocompromised hospitalized patients. The mucosal-cutaneous forms—particularly vaginal infections—have a high prevalence. Vaginitis caused by Candida species is the second most common vaginal infection. Hence, candidiasis is a major subject for research, including experimental in vivo models to study pathogenesis, prevention, or therapy of the disease. The following review article will focus on various experimental in vivo models in different laboratory animals, such as mammals (mice, rats, rabbits, the fruit fly–Drosophila melanogaster, the larvae of the moth Galleria mellonella, or the free-living nematode Caenorhabditis elegans. The review will describe the induction of the different clinical forms of candidiasis in the various models and the validity of such models in mimicking the human clinical situations. The use of such models for the assessment of antifungal drugs, evaluation of potential vaccines to protect before candidiasis, exploration of Candida virulence factors, and comparison of pathogenicity of different Candida species will be included in the review. All of the above will be reported as based on published studies of numerous investigators as well as on the research of the author and his group.

  5. Effects of traction on the blood circulation of femoral head: DSA study on a canine model

    International Nuclear Information System (INIS)

    Yang Xiujun; Xiao Jian; Ren Qile; Fu Shiping; Li Wei; Xiao Xiangsheng

    2010-01-01

    , group K, M and P, Group N and Q was 437.48, 30.25, 29.04, 132.69, 143.73, 25.20, respectively, and their P value was all <0.01. F value of femoral head circulation time among group A and B, group B and C, group B, D, E, F and G, Group H, I, J, L and O, group K, M and P, Group N and Q was 386.26, 31.83, 22.43, 141.94, 119.69, 21.68, respectively, and their P value was all <0.01. Conclusions: Traction could lead to ischemic response and circulation disorder of canine femoral head. The longer the traction time or the bigger the traction weight was, the poorer the femoral head perfusion and the longer the femoral head circulation time were, and the slower they recovered. DSA could directly reflect these changes in the femoral head with these angioarchitectural and hemodynamic indexes. (authors)

  6. Experimental modeling of eddy current inspection capabilities

    International Nuclear Information System (INIS)

    Junker, W.R.; Clark, W.G.

    1984-01-01

    This chapter examines the experimental modeling of eddy current inspection capabilities based upon the use of liquid mercury samples designed to represent metal components containing discontinuities. A brief summary of past work with mercury modeling and a detailed discussion of recent experiments designed to further evaluate the technique are presented. The main disadvantages of the mercury modeling concept are that mercury is toxic and must be handled carefully, liquid mercury can only be used to represent nonferromagnetic materials, and wetting and meniscus problems can distort the effective size of artificial discontinuities. Artificial discontinuities placed in a liquid mercury sample can be used to represent discontinuities in solid metallic structures. Discontinuity size and type cannot be characterized from phase angle and signal amplitude data developed with a surface scanning, pancake-type eddy current probe. It is concluded that the mercury model approach can greatly enhance the overall understanding and applicability of eddy current inspection techniques

  7. Endometriose: modelo experimental em ratas Endometriosis: experimental model in rats

    Directory of Open Access Journals (Sweden)

    Eduardo Schor

    1999-06-01

    Full Text Available Objetivo: divulgar a metodologia da indução de endometriose experimental em animais de laboratório. Método: utilizamos ratas albinas, virgens, adultas de aproximadamente três meses de idade, que foram inicialmente anestesiadas pelo éter etílico. Aberta a cavidade abdominal, identificamos os cornos uterinos e retiramos um fragmento de aproximadamente 4 cm do corno uterino direito. Esse fragmento foi mergulhado em solução fisiológica e sob lupa estereoscópica foi separado o endométrio do miométrio e feitos retângulos de aproximadamente 4 por 5 mm. Esses foram fixados por meio de fio de sutura, sobre vasos sangüíneos visíveis a olho nu, na parede lateral do abdômen, tomando-se sempre o cuidado de manter a porção do endométrio livre voltada para a luz da cavidade abdominal. Após 21 dias os animais foram novamente operados para verificarmos o tamanho dos implantes e para retirada do endométrio ectópico para análise histológica. Resultados: macroscopicamente observamos crescimento significativo dos implantes endometriais. Ao exame microscópico pudemos observar a presença de epitélio glandular e estroma semelhantes ao do endométrio tópico. Conclusões: o modelo utilizado reproduz a doença, em ratas, sendo método auxiliar de valia para estudar esta afecção, principalmente a ação de medicamentos sobre esses implantes.Purpose: to demonstrate the experimental endometriosis induction in animals. Method: we used adult female Wistar rats weighing 200 - 250 g anesthetized with ethyl ether to open the abdominal cavity. After identifying the uterine horns, we removed an approximately 4 cm fragment from the right uterine horn. This fragment was placed in physiological saline and, with the aid of a stereoscopic magnifying glass, the endometrium was separated from the myometrium and cut into rectangles of approximately 4 x 5 mm. These rectangles were fastened to the lateral abdominal wall near great blood vessels, taking care

  8. The difference of canine, first and second premolar tooth size resulted from cone beam computed tomography imaging with Moyers Prediction Table on the working study model

    Directory of Open Access Journals (Sweden)

    Julies Hariani Sugiaman

    2011-03-01

    Full Text Available Model study is one of the standard orthodontic components which is important for diagnosis and treatment plan, but in some patients with the high gag reflex, it will be difficult to get this kind of study models. The existence of a new device which is able to show the condition of patients' mouth in three space areas (axial, sagittal, and coronal is expected to be an alternative when a study model is difficult to get. The purpose of this study is to find out whether or not there are any differences on the size of canine's mesiodistal, first and second premolar resulted from CBCT imaging with Moyers analysis on the study models. The method of the research is comparative descriptive. Measurements are made on 10 CBCT imaging results and 10 study models. The mesiodistal size, the result of CBCT imaging is measured by the available computer program and also the mesiodistal size of the study models is measured using a sliding compass, and then the size of canines, first and second premolar teeth resulted from CBCT imaging are compared to the result of Moyers method analysis on the study models. The t-test is used to find out if there is a difference between teeth size value between the CBCT imaging with the study models. The significance is determined based on the p-value t table.

  9. Absolute quantitation of myocardial blood flow with 201Tl and dynamic SPECT in canine: optimisation and validation of kinetic modelling

    International Nuclear Information System (INIS)

    Iida, Hidehiro; Kim, Kyeong-Min; Nakazawa, Mayumi; Sohlberg, Antti; Zeniya, Tsutomu; Hayashi, Takuya; Watabe, Hiroshi; Eberl, Stefan; Tamura, Yoshikazu; Ono, Yukihiko

    2008-01-01

    201 Tl has been extensively used for myocardial perfusion and viability assessment. Unlike 99m Tc-labelled agents, such as 99m Tc-sestamibi and 99m Tc-tetrofosmine, the regional concentration of 201 Tl varies with time. This study is intended to validate a kinetic modelling approach for in vivo quantitative estimation of regional myocardial blood flow (MBF) and volume of distribution of 201 Tl using dynamic SPECT. Dynamic SPECT was carried out on 20 normal canines after the intravenous administration of 201 Tl using a commercial SPECT system. Seven animals were studied at rest, nine during adenosine infusion, and four after beta-blocker administration. Quantitative images were reconstructed with a previously validated technique, employing OS-EM with attenuation-correction, and transmission-dependent convolution subtraction scatter correction. Measured regional time-activity curves in myocardial segments were fitted to two- and three-compartment models. Regional MBF was defined as the influx rate constant (K 1 ) with corrections for the partial volume effect, haematocrit and limited first-pass extraction fraction, and was compared with that determined from radio-labelled microspheres experiments. Regional time-activity curves responded well to pharmacological stress. Quantitative MBF values were higher with adenosine and decreased after beta-blocker compared to a resting condition. MBFs obtained with SPECT (MBF SPECT ) correlated well with the MBF values obtained by the radio-labelled microspheres (MBF MS ) (MBF SPECT = -0.067 + 1.042 x MBF MS , p 201 Tl and dynamic SPECT. (orig.)

  10. Canine models of inherited bleeding disorders in the development of coagulation assays, novel protein replacement and gene therapies.

    Science.gov (United States)

    Nichols, T C; Hough, C; Agersø, H; Ezban, M; Lillicrap, D

    2016-05-01

    Animal models of inherited bleeding disorders are important for understanding disease pathophysiology and are required for preclinical assessment of safety prior to testing of novel therapeutics in human and veterinary medicine. Experiments in these animals represent important translational research aimed at developing safer and better treatments, such as plasma-derived and recombinant protein replacement therapies, gene therapies and immune tolerance protocols for antidrug inhibitory antibodies. Ideally, testing is done in animals with the analogous human disease to provide essential safety information, estimates of the correct starting dose and dose response (pharmacokinetics) and measures of efficacy (pharmacodynamics) that guide the design of human trials. For nearly seven decades, canine models of hemophilia, von Willebrand disease and other inherited bleeding disorders have not only informed our understanding of the natural history and pathophysiology of these disorders but also guided the development of novel therapeutics for use in humans and dogs. This has been especially important for the development of gene therapy, in which unique toxicities such as insertional mutagenesis, germ line gene transfer and viral toxicities must be assessed. There are several issues regarding comparative medicine in these species that have a bearing on these studies, including immune reactions to xenoproteins, varied metabolism or clearance of wild-type and modified proteins, and unique tissue tropism of viral vectors. This review focuses on the results of studies that have been performed in dogs with inherited bleeding disorders that closely mirror the human condition to develop safe and effective protein and gene-based therapies that benefit both species. © 2016 International Society on Thrombosis and Haemostasis.

  11. Experimental animal modelling for TB vaccine development

    Directory of Open Access Journals (Sweden)

    Pere-Joan Cardona

    2017-03-01

    Full Text Available Research for a novel vaccine to prevent tuberculosis is an urgent medical need. The current vaccine, BCG, has demonstrated a non-homogenous efficacy in humans, but still is the gold standard to be improved upon. In general, the main indicator for testing the potency of new candidates in animal models is the reduction of the bacillary load in the lungs at the acute phase of the infection. Usually, this reduction is similar to that induced by BCG, although in some cases a weak but significant improvement can be detected, but none of candidates are able to prevent establishment of infection. The main characteristics of several laboratory animals are reviewed, reflecting that none are able to simulate the whole characteristics of human tuberculosis. As, so far, no surrogate of protection has been found, it is important to test new candidates in several models in order to generate convincing evidence of efficacy that might be better than that of BCG in humans. It is also important to investigate the use of “in silico” and “ex vivo” models to better understand experimental data and also to try to replace, or at least reduce and refine experimental models in animals.

  12. Models for Experimental High Density Housing

    Science.gov (United States)

    Bradecki, Tomasz; Swoboda, Julia; Nowak, Katarzyna; Dziechciarz, Klaudia

    2017-10-01

    The article presents the effects of research on models of high density housing. The authors present urban projects for experimental high density housing estates. The design was based on research performed on 38 examples of similar housing in Poland that have been built after 2003. Some of the case studies show extreme density and that inspired the researchers to test individual virtual solutions that would answer the question: How far can we push the limits? The experimental housing projects show strengths and weaknesses of design driven only by such indexes as FAR (floor attenuation ratio - housing density) and DPH (dwellings per hectare). Although such projects are implemented, the authors believe that there are reasons for limits since high index values may be in contradiction to the optimum character of housing environment. Virtual models on virtual plots presented by the authors were oriented toward maximising the DPH index and DAI (dwellings area index) which is very often the main driver for developers. The authors also raise the question of sustainability of such solutions. The research was carried out in the URBAN model research group (Gliwice, Poland) that consists of academic researchers and architecture students. The models reflect architectural and urban regulations that are valid in Poland. Conclusions might be helpful for urban planners, urban designers, developers, architects and architecture students.

  13. Experimental data and dose-response models

    International Nuclear Information System (INIS)

    Ullrich, R.L.

    1985-01-01

    Dose-response relationships for radiation carcinogenesis have been of interest to biologists, modelers, and statisticians for many years. Despite his interest there are few instances in which there are sufficient experimental data to allow the fitting of various dose-response models. In those experimental systems for which data are available the dose-response curves for tumor induction for the various systems cannot be described by a single model. Dose-response models which have been observed following acute exposures to gamma rays include threshold, quadratic, and linear models. Data on sex, age, and environmental influences of dose suggest a strong role of host factors on the dose response. With decreasing dose rate the effectiveness of gamma ray irradiation tends to decrease in essentially every instance. In those cases in which the high dose rate dose response could be described by a quadratic model, the effect of dose rate is consistent with predictions based on radiation effects on the induction of initial events. Whether the underlying reasons for the observed dose-rate effect is a result of effects on the induction of initial events or is due to effects on the subsequent steps in the carcinogenic process is unknown. Information on the dose response for tumor induction for high LET (linear energy transfer) radiations such as neutrons is even more limited. The observed dose and dose rate data for tumor induction following neutron exposure are complex and do not appear to be consistent with predictions based on models for the induction of initial events

  14. Authentication of primordial characteristics of the CLBL-1 cell line prove the integrity of a canine B-cell lymphoma in a murine in vivo model.

    Directory of Open Access Journals (Sweden)

    Barbara C Rütgen

    Full Text Available Cell lines are key tools in cancer research allowing the generation of neoplasias in animal models resembling the initial tumours able to mimic the original neoplasias closely in vivo. Canine lymphoma is the major hematopoietic malignancy in dogs and considered as a valuable spontaneous large animal model for human Non-Hodgkin's Lymphoma (NHL. Herein we describe the establishment and characterisation of an in vivo model using the canine B-cell lymphoma cell line CLBL-1 analysing the stability of the induced tumours and the ability to resemble the original material. CLBL-1 was injected into Rag2(-/-γ(c (-/- mice. The generated tumor material was analysed by immunophenotyping and histopathology and used to establish the cell line CLBL-1M. Both cell lines were karyotyped for detection of chromosomal aberrations. Additionally, CLBL-1 was stimulated with IL-2 and DSP30 as described for primary canine B-cell lymphomas and NHL to examine the stimulatory effect on cell proliferation. CLBL-1 in vivo application resulted in lymphoma-like disease and tumor formation. Immunophenotypic analysis of tumorous material showed expression of CD45(+, MHCII(+, CD11a(+ and CD79αcy(+. PARR analysis showed positivity for IgH indicating a monoclonal character. These cytogenetic, molecular, immunophenotypical and histological characterisations of the in vivo model reveal that the induced tumours and thereof generated cell line resemble closely the original material. After DSP30 and IL-2 stimulation, CLBL-1 showed to respond in the same way as primary material. The herein described CLBL-1 in vivo model provides a highly stable tool for B-cell lymphoma research in veterinary and human medicine allowing various further in vivo studies.

  15. Authentication of primordial characteristics of the CLBL-1 cell line prove the integrity of a canine B-cell lymphoma in a murine in vivo model.

    Science.gov (United States)

    Rütgen, Barbara C; Willenbrock, Saskia; Reimann-Berg, Nicola; Walter, Ingrid; Fuchs-Baumgartinger, Andrea; Wagner, Siegfried; Kovacic, Boris; Essler, Sabine E; Schwendenwein, Ilse; Nolte, Ingo; Saalmüller, Armin; Murua Escobar, Hugo

    2012-01-01

    Cell lines are key tools in cancer research allowing the generation of neoplasias in animal models resembling the initial tumours able to mimic the original neoplasias closely in vivo. Canine lymphoma is the major hematopoietic malignancy in dogs and considered as a valuable spontaneous large animal model for human Non-Hodgkin's Lymphoma (NHL). Herein we describe the establishment and characterisation of an in vivo model using the canine B-cell lymphoma cell line CLBL-1 analysing the stability of the induced tumours and the ability to resemble the original material. CLBL-1 was injected into Rag2(-/-)γ(c) (-/-) mice. The generated tumor material was analysed by immunophenotyping and histopathology and used to establish the cell line CLBL-1M. Both cell lines were karyotyped for detection of chromosomal aberrations. Additionally, CLBL-1 was stimulated with IL-2 and DSP30 as described for primary canine B-cell lymphomas and NHL to examine the stimulatory effect on cell proliferation. CLBL-1 in vivo application resulted in lymphoma-like disease and tumor formation. Immunophenotypic analysis of tumorous material showed expression of CD45(+), MHCII(+), CD11a(+) and CD79αcy(+). PARR analysis showed positivity for IgH indicating a monoclonal character. These cytogenetic, molecular, immunophenotypical and histological characterisations of the in vivo model reveal that the induced tumours and thereof generated cell line resemble closely the original material. After DSP30 and IL-2 stimulation, CLBL-1 showed to respond in the same way as primary material. The herein described CLBL-1 in vivo model provides a highly stable tool for B-cell lymphoma research in veterinary and human medicine allowing various further in vivo studies.

  16. The placement of Y-shaped titanium-nickel memory alloy stent in the carina: a fundamental study in experimental canines

    International Nuclear Information System (INIS)

    Bian Wei; Shen Che

    2010-01-01

    Objective: To investigate the pathological changes of local airway tissue after inserting Yshaped titanium-nickel memory alloy stent in carina, and to evaluate CT three-dimensional reconstruction technique in postoperative and follow-up observation. Methods: Twelve healthy adult canines were enrolled in this study. Based on the information of the carina obtained from CT three-dimensional reconstruction images, the preparation of Y-shape netlike stent was made by knitting method with single Ni-Ti memory alloy wire. The stent was then inserted in canine's carina with the help of a releasing system. After the operation fiberbronchoscopy and CT three-dimensional reconstruction were performed. The animals were sacrificed 12 weeks after the procedure and the bronchus of the stenting segment was removed and sent for histopathologic examination. Results: Technical success was achieved in all canines with the stent right in the carina. The airway remained unobstructed 12 weeks after the procedure. Histopathologic examination revealed that the stent became partial epithelialization. Conclusion: The Y-shaped titanium-nickel memory alloy stent has good histocompatibility and physicochemical stability and no re-stenosis of the airway develops in the follow-up period of three months. The stent-releasing technique is easy and simple. As a non-invasive and convenient exam, CT three-dimensional reconstruction technique is of great value in postoperative follow-up observation. (authors)

  17. Surface physics theoretical models and experimental methods

    CERN Document Server

    Mamonova, Marina V; Prudnikova, I A

    2016-01-01

    The demands of production, such as thin films in microelectronics, rely on consideration of factors influencing the interaction of dissimilar materials that make contact with their surfaces. Bond formation between surface layers of dissimilar condensed solids-termed adhesion-depends on the nature of the contacting bodies. Thus, it is necessary to determine the characteristics of adhesion interaction of different materials from both applied and fundamental perspectives of surface phenomena. Given the difficulty in obtaining reliable experimental values of the adhesion strength of coatings, the theoretical approach to determining adhesion characteristics becomes more important. Surface Physics: Theoretical Models and Experimental Methods presents straightforward and efficient approaches and methods developed by the authors that enable the calculation of surface and adhesion characteristics for a wide range of materials: metals, alloys, semiconductors, and complex compounds. The authors compare results from the ...

  18. NS5806 partially restores action potential duration but fails to ameliorate calcium transient dysfunction in a computational model of canine heart failure.

    Science.gov (United States)

    Maleckar, Mary M; Lines, Glenn T; Koivumäki, Jussi T; Cordeiro, Jonathan M; Calloe, Kirstine

    2014-11-01

    The study investigates how increased Ito, as mediated by the activator NS5806, affects excitation-contraction coupling in chronic heart failure (HF). We hypothesized that restoring spike-and-dome morphology of the action potential (AP) to a healthy phenotype would be insufficient to restore the intracellular Ca(2) (+) transient (CaT), due to HF-induced remodelling of Ca(2+) handling. An existing mathematical model of the canine ventricular myocyte was modified to incorporate recent experimental data from healthy and failing myocytes, resulting in models of both healthy and HF epicardial, midmyocardial, and endocardial cell variants. Affects of NS5806 were also included in HF models through its direct interaction with Kv4.3 and Kv1.4. Single-cell simulations performed in all models (control, HF, and HF + drug) and variants (epi, mid, and endo) assessed AP morphology and underlying ionic processes with a focus on calcium transients (CaT), how these were altered in HF across the ventricular wall, and the subsequent effects of varying compound concentration in HF. Heart failure model variants recapitulated a characteristic increase in AP duration (APD) in the disease. The qualitative effects of application of half-maximal effective concentration (EC50) of NS5806 on APs and CaT are heterogeneous and non-linear. Deepening in the AP notch with drug is a direct effect of the activation of Ito; both Ito and consequent alteration of IK1 kinetics cause decrease in AP plateau potential. Decreased APD50 and APD90 are both due to altered IK1. Analysis revealed that drug effects depend on transmurality. Ca(2+) transient morphology changes-increased amplitude and shorter time to peak-are due to direct increase in ICa,L and indirect larger SR Ca(2+) release subsequent to Ito activation. Downstream effects of a compound acting exclusively on sarcolemmal ion channels are difficult to predict. Remediation of APD to pre-failing state does not ameliorate dysfunction in CaT; however

  19. Upregulation of CB2 receptors in reactive astrocytes in canine degenerative myelopathy, a disease model of amyotrophic lateral sclerosis

    Science.gov (United States)

    Fernández-Trapero, María; Espejo-Porras, Francisco; Rodríguez-Cueto, Carmen; Coates, Joan R.; Pérez-Díaz, Carmen; de Lago, Eva; Fernández-Ruiz, Javier

    2017-01-01

    ABSTRACT Targeting of the CB2 receptor results in neuroprotection in the SOD1G93A mutant mouse model of amyotrophic lateral sclerosis (ALS). The neuroprotective effects of CB2 receptors are facilitated by their upregulation in the spinal cord of the mutant mice. Here, we investigated whether similar CB2 receptor upregulation, as well as parallel changes in other endocannabinoid elements, is evident in the spinal cord of dogs with degenerative myelopathy (DM), caused by mutations in the superoxide dismutase 1 gene (SOD1). We used well-characterized post-mortem spinal cords from unaffected and DM-affected dogs. Tissues were used first to confirm the loss of motor neurons using Nissl staining, which was accompanied by glial reactivity (elevated GFAP and Iba-1 immunoreactivity). Next, we investigated possible differences in the expression of endocannabinoid genes measured by qPCR between DM-affected and control dogs. We found no changes in expression of the CB1 receptor (confirmed with CB1 receptor immunostaining) or NAPE-PLD, DAGL, FAAH and MAGL enzymes. In contrast, CB2 receptor levels were significantly elevated in DM-affected dogs determined by qPCR and western blotting, which was confirmed in the grey matter using CB2 receptor immunostaining. Using double-labelling immunofluorescence, CB2 receptor immunolabelling colocalized with GFAP but not Iba-1, indicating upregulation of CB2 receptors on astrocytes in DM-affected dogs. Our results demonstrate a marked upregulation of CB2 receptors in the spinal cord in canine DM, which is concentrated in activated astrocytes. Such receptors could be used as a potential target to enhance the neuroprotective effects exerted by these glial cells. PMID:28069688

  20. Upregulation of CB2 receptors in reactive astrocytes in canine degenerative myelopathy, a disease model of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    María Fernández-Trapero

    2017-05-01

    Full Text Available Targeting of the CB2 receptor results in neuroprotection in the SOD1G93A mutant mouse model of amyotrophic lateral sclerosis (ALS. The neuroprotective effects of CB2 receptors are facilitated by their upregulation in the spinal cord of the mutant mice. Here, we investigated whether similar CB2 receptor upregulation, as well as parallel changes in other endocannabinoid elements, is evident in the spinal cord of dogs with degenerative myelopathy (DM, caused by mutations in the superoxide dismutase 1 gene (SOD1. We used well-characterized post-mortem spinal cords from unaffected and DM-affected dogs. Tissues were used first to confirm the loss of motor neurons using Nissl staining, which was accompanied by glial reactivity (elevated GFAP and Iba-1 immunoreactivity. Next, we investigated possible differences in the expression of endocannabinoid genes measured by qPCR between DM-affected and control dogs. We found no changes in expression of the CB1 receptor (confirmed with CB1 receptor immunostaining or NAPE-PLD, DAGL, FAAH and MAGL enzymes. In contrast, CB2 receptor levels were significantly elevated in DM-affected dogs determined by qPCR and western blotting, which was confirmed in the grey matter using CB2 receptor immunostaining. Using double-labelling immunofluorescence, CB2 receptor immunolabelling colocalized with GFAP but not Iba-1, indicating upregulation of CB2 receptors on astrocytes in DM-affected dogs. Our results demonstrate a marked upregulation of CB2 receptors in the spinal cord in canine DM, which is concentrated in activated astrocytes. Such receptors could be used as a potential target to enhance the neuroprotective effects exerted by these glial cells.

  1. Randomized comparison of intra-arterial and intravenous thrombolysis in a canine model of acute basilar artery thrombosis

    International Nuclear Information System (INIS)

    Qureshi, A.I.; Yahia, A.M.; Boulos, A.S.; Hanel, R.A.; Suri, M.F.K.; Hopkins, L.N.; Alberico, R.A.

    2004-01-01

    We compared the rates of recanalization cerebral infarct and hemorrhage between intra-arterial (IA) reteplase and intravenous (IV) alteplase thrombolysis in a canine model of basilar artery thrombosis. Thrombosis was induced by injecting a clot in the basilar artery of 13 anesthetized dogs via superselective catheterization. The animals were randomized in a blinded fashion, 2 h after clot injection and verification of arterial occlusion, to receive IV alteplase 0.9 mg/kg over 60 min and IA placebo, or IA reteplase 0.09 units/kg over 20 min, equivalent to one-half the alteplase dose, and IV placebo. Recanalization was studied for 6 h after treatment with serial angiography; the images were later graded in a blinded fashion. Blinded interpretation of postmortem MRI was performed to assess the presence of brain infarcts and/or hemorrhage. At 3 h after initiation of treatment, partial or complete recanalization was observed in one of six dogs in the IV alteplase group and in five of seven in the IA reteplase group (P = 0.08). At 6 h, no significant difference in partial or complete recanalization was observed between the groups (two of six vs. five of seven; P = 0.20). Postmortem MRI revealed infarcts in four of six animals treated with IV alteplase and three of seven treated with IA reteplase (P = 0.4). Intracerebral hemorrhage was more common in the IV alteplase group (four of six vs. none of seven; P = 0.02). This study thus suggests that IA thrombolysis affords a recanalization rate similar to that of IV thrombolysis, but with a lower rate of intracerebral hemorrhage. (orig.)

  2. Superficial tension: experimental model with simple materials

    Directory of Open Access Journals (Sweden)

    Tintori Ferreira, María Alejandra

    2012-09-01

    Full Text Available In this work appears a didactic offer based on an experimental activity using materials of very low cost, orientated to achieving that the student understand and interpret the phenomenon of superficial tension together with the importance of the modeling in sciences. It has as principal aim of education bring the student over to the mechanics of the static fluids and the intermolecular forces, combining scientific contents with questions near to the student what provides an additional motivation to the reflection of the scientific investigation.

  3. The establishment of atrial septal defect model with interventional management canine: its applied anatomy and technical points

    International Nuclear Information System (INIS)

    Zhu Yufeng; Huang Xinmiao; Bei Yuan; Wang Wei; Hu Jianqiang; Qin Yongwen

    2010-01-01

    Objective: To provide the relevant applied anatomic information for the preparation of atrial septal defect (ASD) model with transcatheter management in canine,and to discuss the technical points in making ASD model under DSA guidance. Methods: Anatomical measurements of the heart specimens,which were obtained from 15 healthy adult hybrid dogs (9 males and 6 females), were performed, from which the relevant anatomic parameters of the atrial septum were calculated. Cardiac 3D reconstruction with 64-sliced spiral CT scan was carried out in 5 dogs and the results were analyzed. According to the trans-illuminated position and angle obtained from 3D reconstruction images both the puncturing of the atrial septum with Brokenbrough needle and the balloon dilatation under fluoroscopic guidance were conducted in 20 dogs (body weight 17 -22 kg) to prepare ASD model. Results: The length and the width of the interauricular septum were (17.8 ± 4.3) mm and (14.5 ± 3.8) mm, respectively. The oval fossa was (11.2 ± 2.7) mm long and (8.7±1.9) mm wide. The distance from the central point of oval fossa to the central point of the orifice of coronary sinus was (7.2 ± 1.3) mm, which was (9.9 ± 1.5) mm to the center of the membranous atrial septum, (13.6 ± 3.1) mm to the middle point of septal tricuspid valve, (12.1 ± 2.3) mm to the central point of the bottom of aortic eminence and (11.3 ± 1.9) mm to the middle point of anterior bicuspid valve. The angle between atrial septal plane and sagittal plane was 15 degree ± 5 degree, and the angle between atrial septal plane and coronal plane was 75 degree ± 5 degree. Thus, the puncture of the interauricular septum was carried out with the dog in right anterior oblique position at 75 degree ± 5 degree. Of the total 20 dogs, ASD model was successfully established in 18, failure of the puncturing occurred in the remaining two, of which one died of cardiac tamponade after the procedure and the other one died of mistakenly puncturing

  4. Correlation between intravoxel incoherent motion magnetic resonance imaging derived metrics and serum soluble CD40 ligand level in an embolic canine stroke model

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xiao Quan; Wu, Chen Jiang; Lu, Shan Shan; Gao, Qian Qian; Zu, Qing Quan; Liu, Xing Long; Shi, Hai Bin; Liu, Sheng [Dept. of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2017-09-15

    To determine the relationship between intravoxel incoherent motion (IVIM) imaging derived quantitative metrics and serum soluble CD40 ligand (sCD40L) level in an embolic canine stroke model. A middle cerebral artery occlusion model was established in 24 beagle dogs. Experimental dogs were divided into low- and high-sCD40L group according to serum sCD40L level at 4.5 hours after establishing the model. IVIM imaging was scanned at 4.5 hours after model establishment using 10 b values ranging from 0 to 900 s/mm{sup 2}. Quantitative metrics diffusion coefficient (D), pseudodiffusion coefficient (D{sup *}), and perfusion fraction (f) of ischemic lesions were calculated. Quantitative metrics of ischemic lesions were normalized by contralateral hemisphere using the following formula: normalized D = D{sub stroke} / D{sub contralateral}. Differences in IVIM metrics between the low- and high-sCD40L groups were compared using t test. Pearson's correlation analyses were performed to determine the relationship between IVIM metrics and serum sCD40L level. The high-sCD40L group showed significantly lower f and normalized f values than the low-sCD40L group (f, p < 0.001; normalized f, p < 0.001). There was no significant difference in D{sup *}, normalized D{sup *}, D, or normalized D value between the two groups (All p > 0.05). Both f and normalized f values were negatively correlated with serum sCD40L level (f, r = −0.789, p < 0.001; normalized f, r = −0.823, p < 0.001). However, serum sCD40L level had no significant correlation with D{sup *}, normalized D{sup *}, D, or normalized D (All p > 0.05). The f value derived from IVIM imaging was negatively correlated with serum sCD40L level. f value might serve as a potential imaging biomarker to assess the formation of microvascular thrombosis in hyperacute period of ischemic stroke.

  5. Use of quantitative real-time RT-PCR to investigate the correlation between viremia and viral shedding of canine distemper virus, and infection outcomes in experimentally infected dogs.

    Science.gov (United States)

    Sehata, Go; Sato, Hiroaki; Ito, Toshihiro; Imaizumi, Yoshitaka; Noro, Taichi; Oishi, Eiji

    2015-07-01

    We used real-time RT-PCR and virus titration to examine canine distemper virus (CDV) kinetics in peripheral blood and rectal and nasal secretions from 12 experimentally infected dogs. Real-time RT-PCR proved extremely sensitive, and the correlation between the two methods for rectal and nasal (r=0.78, 0.80) samples on the peak day of viral RNA was good. Although the dogs showed diverse symptoms, viral RNA kinetics were similar; the peak of viral RNA in the symptomatic dogs was consistent with the onset of symptoms. These results indicate that real-time RT-PCR is sufficiently sensitive to monitor CDV replication in experimentally infected dogs regardless of the degree of clinical manifestation and suggest that the peak of viral RNA reflects active CDV replication.

  6. Experimental model of bladder instability in rabbits

    Directory of Open Access Journals (Sweden)

    Balasteghin K.T.

    2003-01-01

    Full Text Available OBJECTIVE: Propose a new experimental model of bladder instability in rabbits after partial bladder obstruction. MATERIALS AND METHODS: Thirty North Folk male rabbits, weighting 1,700 to 2,820 g (mean: 2,162 g were studied. The animals were distributed in 2 experimental groups, formed by 15 rabbits each: Group 1 - clinical control. In this group there was no surgical intervention; Group 2 - bladder outlet obstruction. In this group, after anesthetizing the animal, urethral cannulation with Foley catheter 10F was performed and then an adjustable plastic bracelet was passed around the bladder neck. It was then adjusted in order to not constrict the urethra. The following parameters were studied in M1 - pre-operative period; M2 - 4 weeks post-operatively moments: 1- urine culture; 2- cystometric study; 3- serum creatinine and BUN. RESULTS: Bladder weight was 2.5 times larger in the group with obstruction than in the control group. Cystometric evaluation showed a significant increase in maximal vesical volume in the final moment at Group G2. However, there was no statistically significant difference among the groups studied. There was no statistically significant difference between maximal detrusor pressure and vesical compliance in the different moments or in the studied groups. There was an absence of uninhibited detrusor contractions in all the animals in group 1, and involuntary contractions were detected in 93% of group 2 animals. There was no significant variation in BUN and serum creatinine either among the groups or in the same group. CONCLUSIONS: We observed in the group with obstruction a bladder weight 2.5 higher than normal bladders. We detected involuntary contractions in 93% of the animals in group 2, establishing this experimental model as appropriate to secondary bladder instability and partial bladder outlet obstruction.

  7. Experimental Oral Candidiasis in Animal Models

    Science.gov (United States)

    Samaranayake, Yuthika H.; Samaranayake, Lakshman P.

    2001-01-01

    Oral candidiasis is as much the final outcome of the vulnerability of the host as of the virulence of the invading organism. We review here the extensive literature on animal experiments mainly appertaining to the host predisposing factors that initiate and perpetuate these infections. The monkey, rat, and mouse are the choice models for investigating oral candidiasis, but comparisons between the same or different models appear difficult, because of variables such as the study design, the number of animals used, their diet, the differences in Candida strains, and the duration of the studies. These variables notwithstanding, the following could be concluded. (i) The primate model is ideal for investigating Candida-associated denture stomatitis since both erythematous and pseudomembranous lesions have been produced in monkeys with prosthetic plates; they are, however, expensive and difficult to obtain and maintain. (ii) The rat model (both Sprague-Dawley and Wistar) is well proven for observing chronic oral candidal colonization and infection, due to the ease of breeding and handling and their ready availability. (iii) Mice are similar, but in addition there are well characterized variants simulating immunologic and genetic abnormalities (e.g., athymic, euthymic, murine-acquired immune deficiency syndrome, and severe combined immunodeficient models) and hence are used for short-term studies relating the host immune response and oral candidiasis. Nonetheless, an ideal, relatively inexpensive model representative of the human oral environment in ecological and microbiological terms is yet to be described. Until such a model is developed, researchers should pay attention to standardization of the experimental protocols described here to obtain broadly comparable and meaningful data. PMID:11292645

  8. Experimental models of chronic subdural hematoma.

    Science.gov (United States)

    D'Abbondanza, Josephine A; Loch Macdonald, R

    2014-02-01

    Chronic subdural hematoma (CSDH) is a common neurosurgical problem. Most studies of pathogenesis and treatment involve humans. Advances in understanding of human diseases may be made using animal models. We reviewed all animal models of CSDH and report here their results, conclusions and limitations in order to set a baseline upon which further advanced experimental work related to this disease can be made. PubMed, Medline, Embase and ISI Web of Knowledge were searched with no time limits using the keyword 'chronic subdural hematoma' and MeSH term 'hematoma, subdural, chronic'. The authors reviewed all papers written related to this disease and selected all publications involving animals. There were no other restrictions. The findings and conclusions of the papers are summarized here. No formal analysis was done because of the variation in species used, methods for induction of CSDH, times of assessment and reporting of results. Attempts to create CSDH have been made in mice, rats, cats, dogs and monkeys. Methods include injection or surgical implantation of clotted blood or various other blood products and mixtures into the potential subdural space or the subcutaneous space. No intracranial model produced a progressively expanding CSDH. Transient hematoma expansion with liquification could be produced by subcutaneous injections in some models. Spontaneous subdural blood collections were found after creation of hydrocephalus in mice by systemic injection of the neurotoxin, 6-aminonicotinamide. The histology of the hematoma membranes in several models resembles the appearance in humans. None of the models has been replicated since its first description. We did not find a report of a reproducible, well-described animal model of human CSDH.

  9. Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Antitumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies.

    Science.gov (United States)

    Monjazeb, Arta M; Kent, Michael S; Grossenbacher, Steven K; Mall, Christine; Zamora, Anthony E; Mirsoian, Annie; Chen, Mingyi; Kol, Amir; Shiao, Stephen L; Reddy, Abhinav; Perks, Julian R; T N Culp, William; Sparger, Ellen E; Canter, Robert J; Sckisel, Gail D; Murphy, William J

    2016-09-01

    Previous studies demonstrate that intratumoral CpG immunotherapy in combination with radiotherapy acts as an in-situ vaccine inducing antitumor immune responses capable of eradicating systemic disease. Unfortunately, most patients fail to respond. We hypothesized that immunotherapy can paradoxically upregulate immunosuppressive pathways, a phenomenon we term "rebound immune suppression," limiting clinical responses. We further hypothesized that the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO) is a mechanism of rebound immune suppression and that IDO blockade would improve immunotherapy efficacy. We examined the efficacy and immunologic effects of a novel triple therapy consisting of local radiotherapy, intratumoral CpG, and systemic IDO blockade in murine models and a pilot canine clinical trial. In murine models, we observed marked increase in intratumoral IDO expression after treatment with radiotherapy, CpG, or other immunotherapies. The addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T cells in the tumor microenvironment. This triple combination induced systemic antitumor effects, decreasing metastases, and improving survival in a CD8(+) T-cell-dependent manner. We evaluated this novel triple therapy in a canine clinical trial, because spontaneous canine malignancies closely reflect human cancer. Mirroring our mouse studies, the therapy was well tolerated, reduced intratumoral immunosuppression, and induced robust systemic antitumor effects. These results suggest that IDO maintains immune suppression in the tumor after therapy, and IDO blockade promotes a local antitumor immune response with systemic consequences. The efficacy and limited toxicity of this strategy are attractive for clinical translation. Clin Cancer Res; 22(17); 4328-40. ©2016 AACR. ©2016 American Association for Cancer Research.

  10. Allogeneic Transplantation of Periodontal Ligament-Derived Multipotent Mesenchymal Stromal Cell Sheets in Canine Critical-Size Supra-Alveolar Periodontal Defect Model.

    Science.gov (United States)

    Tsumanuma, Yuka; Iwata, Takanori; Kinoshita, Atsuhiro; Washio, Kaoru; Yoshida, Toshiyuki; Yamada, Azusa; Takagi, Ryo; Yamato, Masayuki; Okano, Teruo; Izumi, Yuichi

    2016-01-01

    Periodontitis is a chronic inflammatory disease that induces the destruction of tooth-supporting tissues, followed by tooth loss. Although several approaches have been applied to periodontal regeneration, complete periodontal regeneration has not been accomplished. Tissue engineering using a combination of cells and scaffolds is considered to be a viable alternative strategy. We have shown that autologous transplantation of periodontal ligament-derived multipotent mesenchymal stromal cell (PDL-MSC) sheets regenerates periodontal tissue in canine models. However, the indications for autologous cell transplantation in clinical situations are limited. Therefore, this study evaluated the safety and efficacy of allogeneic transplantation of PDL-MSC sheets using a canine horizontal periodontal defect model. Canine PDL-MSCs were labeled with enhanced green fluorescent protein (EGFP) and were cultured on temperature-responsive dishes. Three-layered cell sheets were transplanted around denuded root surfaces either autologously or allogeneically. A mixture of β-tricalcium phosphate and collagen gel was placed on the bone defects. Eight weeks after transplantation, dogs were euthanized and subjected to microcomputed tomography and histological analyses. RNA and DNA were extracted from the paraffin sections to verify the presence of EGFP at the transplantation site. Inflammatory markers from peripheral blood sera were quantified using an enzyme-linked immunosorbent assay. Periodontal regeneration was observed in both the autologous and the allogeneic transplantation groups. The allogeneic transplantation group showed particularly significant regeneration of newly formed cementum, which is critical for the periodontal regeneration. Serum levels of inflammatory markers from peripheral blood sera showed little difference between the autologous and allogeneic groups. EGFP amplicons were detectable in the paraffin sections of the allogeneic group. These results suggest that

  11. Experimental and theoretical requirements for fuel modelling

    International Nuclear Information System (INIS)

    Gatesoupe, J.P.

    1979-01-01

    From a scientific point of view it may be considered that any event in the life of a fuel pin under irradiation should be perfectly well understood and foreseen from that deterministic point of view, the whole behaviour of the pin maybe analysed and dismantled with a specific function for every component part and each component part related to one basic phenomenon which can be independently studied on pure physical grounds. When extracted from the code structure the subroutine is studied for itself by specialists who try to keep as close as possible to the physics involved in the phenomenon; that often leads to an impressive luxury in details and a subsequent need for many unavailable input data. It might seem more secure to follow that approach since it tries to be firmly based on theoretical grounds. One should think so if the phenomenological situation in the pin were less complex than it is. The codes would not be adequate for off-normal operating conditions since for the accidental transient conditions the key-phenomena would not be the same as for steady-state or slow transient conditions. The orientation given to fuel modelling is based on our two main technological constraints which are: no fuel melting; no cladding failure; no excessive cladding deformation. In this context, the only relevant models are those which have a significant influence on the maximum temperatures in the fuel or on the cladding damage hence the selection between key models and irrelevant models which will next be done. A rather pragmatic view is kept on codification with a special focus on a few determinant aspects of fuel behaviour and no attention to models which are nothing but decorative. Fuel modeling is merely considered as a link between experimental knowledge; it serves as a guide for further improvements in fuel design and as so happens to be quite useful. On this basis the main lacks in of fuel behaviour is described. These are mainly concerning: thermal transfer through

  12. Experimental study and modelling of transient boiling

    International Nuclear Information System (INIS)

    Baudin, Nicolas

    2015-01-01

    A failure in the control system of the power of a nuclear reactor can lead to a Reactivity Initiated Accident in a nuclear power plant. Then, a power peak occurs in some fuel rods, high enough to lead to the coolant film boiling. It leads to an important increase of the temperature of the rod. The possible risk of the clad failure is a matter of interest for the Institut de Radioprotection et de Securite Nucleaire. The transient boiling heat transfer is not yet understood and modelled. An experimental set-up has been built at the Institut de Mecanique des Fluides de Toulouse (IMFT). Subcooled HFE-7000 flows vertically upward in a semi annulus test section. The inner half cylinder simulates the clad and is made of a stainless steel foil, heated by Joule effect. Its temperature is measured by an infrared camera, coupled with a high speed camera for the visualization of the flow topology. The whole boiling curve is studied in steady state and transient regimes: convection, onset of boiling, nucleate boiling, critical heat flux, film boiling and rewetting. The steady state heat transfers are well modelled by literature correlations. Models are suggested for the transient heat flux: the convection and nucleate boiling evolutions are self-similar during a power step. This observation allows to model more complex evolutions, as temperature ramps. The transient Hsu model well represents the onset of nucleate boiling. When the intensity of the power step increases, the film boiling begins at the same temperature but with an increasing heat flux. For power ramps, the critical heat flux decreases while the corresponding temperature increases with the heating rate. When the wall is heated, the film boiling heat transfer is higher than in steady state but it is not understood. A two-fluid model well simulates the cooling film boiling and the rewetting. (author)

  13. Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids

    NARCIS (Netherlands)

    Nantasanti, Sathidpak; Spee, Bart; Kruitwagen, Hedwig S.; Chen, Chen; Geijsen, Niels; Oosterhoff, Loes A.; van Wolferen, Monique E.; Pelaez, Nicolas; Fieten, Hille; Wubbolts, Richard W.; Grinwis, Guy C.; Chan, Jefferson; Huch, Meritxell; Vries, Robert R. G.; Clevers, Hans; de Bruin, Alain; Rothuizen, Jan; Penning, Louis C.; Schotanus, Baukje A.

    2015-01-01

    The recent development of 3D-liver stem cell cultures (hepatic organoids) opens up new avenues for gene and/or stem cell therapy to treat liver disease. To test safety and efficacy, a relevant large animal model is essential but not yet established. Because of its shared pathologies and disease

  14. Assessment of left ventricular mechanical dyssynchrony in left bundle branch block canine model: Comparison between cine and tagged MRI.

    Science.gov (United States)

    Saporito, Salvatore; van Assen, Hans C; Houthuizen, Patrick; Aben, Jean-Paul M M; Strik, Marc; van Middendorp, Lars B; Prinzen, Frits W; Mischi, Massimo

    2016-10-01

    To compare cine and tagged magnetic resonance imaging (MRI) for left ventricular dyssynchrony assessment in left bundle branch block (LBBB), using the time-to-peak contraction timing, and a novel approach based on cross-correlation. We evaluated a canine model dataset (n = 10) before (pre-LBBB) and after induction of isolated LBBB (post-LBBB). Multislice short-axis tagged and cine MRI images were acquired using a 1.5 T scanner. We computed contraction time maps by cross-correlation, based on the timing of radial wall motion and of circumferential strain. Finally, we estimated dyssynchrony as the standard deviation of the contraction time over the different regions of the myocardium. Induction of LBBB resulted in a significant increase in dyssynchrony (cine: 13.0 ± 3.9 msec for pre-LBBB, and 26.4 ± 5.0 msec for post-LBBB, P = 0.005; tagged: 17.1 ± 5.0 msec at for pre-LBBB, and 27.9 ± 9.8 msec for post-LBBB, P = 0.007). Dyssynchrony assessed by cine and tagged MRI were in agreement (r = 0.73, P = 0.0003); differences were in the order of time difference between successive frames of 20 msec (bias: -2.9 msec; limit of agreement: 10.1 msec). Contraction time maps were derived; agreement was found in the contraction patterns derived from cine and tagged MRI (mean difference in contraction time per segment: 3.6 ± 13.7 msec). This study shows that the proposed method is able to quantify dyssynchrony after induced LBBB in an animal model. Cine-assessed dyssynchrony agreed with tagged-derived dyssynchrony, in terms of magnitude and spatial direction. J. MAGN. RESON. IMAGING 2016;44:956-963. © 2016 International Society for Magnetic Resonance in Medicine.

  15. Single-layer versus double-layer laparoscopic intracorporeally sutured gastrointestinal anastomoses in the canine model.

    Science.gov (United States)

    Tavakoli, Azine; Bakhtiari, Jalal; Khalaj, Ali Reza; Gharagozlou, Mohammad Javad; Veshkini, Abbas

    2010-01-01

    The objective of this study was to compare the gross and histopathologic changes following 1- versus 2-layer hand-sewn suture techniques in laparoscopic gastrointestinal anastomosis in dogs. This was an experimental prospective study of 16 healthy mixed breed male and female dogs. Animals were randomly divided into 2 groups. Two-layer side-to-side hand-sewn laparoscopic gastrojejunostomies were performed in group A, so that simple interrupted sutures were placed in the outer layer and simple continuous suture was used in the inner layer. The 1-layer simple continuous anastomosis between the stomach and jejunum was done in group B precisely. Specimen were collected from the sites of anastomosis, and H&E statining was performed for light microscopic studies. All animals survived the surgery. There was no gross inflammation, ischemia, apparent granulation tissue, abscess or fistula formation, leakage or stricture formation, and all sites of anastomosis were patent. Several adhesion formations were found in the abdomen with the higher incidence in the control group. Mean scores of leukocyte infiltration and granulation tissue formation at the sites of anastomosis were statistically insignificant between groups (P>0.05). Gross and histopathologic findings revealed that hand-sewn laparoscopic gastrointestinal anastomosis with the 1-layer suture technique is comparable to the 2-layer suture technique.

  16. Experimental models of autoimmune inflammatory ocular diseases

    Directory of Open Access Journals (Sweden)

    Fabio Gasparin

    2012-04-01

    Full Text Available Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin. Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.

  17. Modeling a nuclear reactor for experimental purposes

    International Nuclear Information System (INIS)

    Berta, V.T.

    1980-01-01

    The Loss-of-Fluid Test (LOFT) Facility is a scale model of a commercial PWR and is as fully functional and operational as the generic commercial counterpart. LOFT was designed and built for experimental purposes as part of the overall NRC reactor safety research program. The purpose of LOFT is to assess the capability of reactor safety systems to perform their intended functions during occurrences of off-normal conditions in a commercial nuclear reactor. Off-normal conditions arising from large and small break loss-of-coolant accidents (LOCA), operational transients, and anticipated transients without scram (ATWS) were to be investigated. This paper describes the LOFT model of the generic PWR and summarizes the experiments that have been conducted in the context of the significant findings involving the complex transient thermal-hydraulics and the consequent effects on the commercial reactor analytical licensing techniques. Through these techniques the validity of the LOFT model as a scaled counterpart of the generic PWR is shown

  18. Ghrelin Suppression and Fat Loss after Left Gastric Artery Embolization in Canine Model

    Energy Technology Data Exchange (ETDEWEB)

    Bawudun, Dilmurat [Xinjiang Medical University, Department of Interventional Radiology, First Affiliated Hospital (China); Xing Yan; Liu Wenya, E-mail: wenyaliu2002@hotmail.com; Huang Yujie [Xinjiang Medical University, Imaging Center, First Affiliated Hospital (China); Ren Weixin [Xinjiang Medical University, Department of Interventional Radiology, First Affiliated Hospital (China); Ma Mei [Xinjiang Medical University, Animal Research Center, First Affiliated Hospital (China); Xu Xiaodong [Xinjiang Medical University, Department of Interventional Radiology, First Affiliated Hospital (China); Teng Gaojun [Southeast University, Department of Radiology, Zhong-da Hospital (China)

    2012-12-15

    Purpose: To evaluate the effects of left gastric artery embolization (LGAE) on plasma ghrelin levels, abdominal fat, and body weight in beagles. Methods: The institutional animal care and use committee approved this study. Fifteen healthy adult beagles (12 male and three female animals) were randomly divided into three experimental groups: LGAE was proceeded with mixed emulsion of bleomycin A{sub 5} hydrochloride and lipiodol (group A), and polyvinyl alcohol particles (group B). Transcatheter saline injections in the left gastric artery were performed as a control. Weight and fasting plasma ghrelin levels were obtained at baseline and at weekly intervals for 8 weeks after the procedure in all animals. All animals were scanned and measured by multidetector computed tomography at baseline and at week 8 for evaluation of abdominal fat. Results: In LGAE-treated animals, plasma ghrelin and body weight significantly decreased compared to control animals (group A: P = 0.007 and P = 0.000; group B: P = 0.004 and P = 0.000, respectively). Subcutaneous fat size was also significantly reduced (P = 0.011 and P = 0.027 for groups A and B, respectively). The decreasing percentage in ghrelin levels at week 6 (peak of recovery) of LGAE-treated animals were negatively correlated with the size of area supplied by left gastric artery (r = -0.693, P = 0.026). Conclusion: LGAE could suppress the plasma concentration of ghrelin, which results in subcutaneous fat size reduction and weight loss. Compensatory ghrelin production might occur in the remnant gastric fundus after LGAE.

  19. Ghrelin Suppression and Fat Loss after Left Gastric Artery Embolization in Canine Model

    International Nuclear Information System (INIS)

    Bawudun, Dilmurat; Xing Yan; Liu Wenya; Huang Yujie; Ren Weixin; Ma Mei; Xu Xiaodong; Teng Gaojun

    2012-01-01

    Purpose: To evaluate the effects of left gastric artery embolization (LGAE) on plasma ghrelin levels, abdominal fat, and body weight in beagles. Methods: The institutional animal care and use committee approved this study. Fifteen healthy adult beagles (12 male and three female animals) were randomly divided into three experimental groups: LGAE was proceeded with mixed emulsion of bleomycin A 5 hydrochloride and lipiodol (group A), and polyvinyl alcohol particles (group B). Transcatheter saline injections in the left gastric artery were performed as a control. Weight and fasting plasma ghrelin levels were obtained at baseline and at weekly intervals for 8 weeks after the procedure in all animals. All animals were scanned and measured by multidetector computed tomography at baseline and at week 8 for evaluation of abdominal fat. Results: In LGAE-treated animals, plasma ghrelin and body weight significantly decreased compared to control animals (group A: P = 0.007 and P = 0.000; group B: P = 0.004 and P = 0.000, respectively). Subcutaneous fat size was also significantly reduced (P = 0.011 and P = 0.027 for groups A and B, respectively). The decreasing percentage in ghrelin levels at week 6 (peak of recovery) of LGAE-treated animals were negatively correlated with the size of area supplied by left gastric artery (r = −0.693, P = 0.026). Conclusion: LGAE could suppress the plasma concentration of ghrelin, which results in subcutaneous fat size reduction and weight loss. Compensatory ghrelin production might occur in the remnant gastric fundus after LGAE.

  20. Periodontal and endodontic pathology delays extraction socket healing in a canine model

    Science.gov (United States)

    2017-01-01

    Purpose The aim of the present exploratory study was to evaluate extraction socket healing at sites with a history of periodontal and endodontic pathology. Methods The mandibular 4th premolar teeth in 5 adult beagle dogs served as experimental units. Periodontal and endodontic lesions were induced in 1 premolar site in each animal using wire ligatures and pulpal exposure over 3 months (diseased sites). The contralateral premolar sites served as healthy controls. The mandibular 4th premolar teeth were then extracted with minimal trauma, followed by careful wound debridement. The animals were sacrificed at days 1, 7, 30, 60, and 90 post-extraction for analysis, and the healing patterns at the healthy and diseased extraction sites were compared using radiography, scanning electron microscopy, histology, and histometry. Results During the first 7 days of healing, a significant presence of inflammatory granulation tissue was noted at the diseased sites (day 1), along with a slightly accelerated rate of fibrin clot resolution on day 7. On day 30, the diseased extraction sites showed a greater percentage of persistent fibrous connective tissue, and an absence of bone marrow formation. In contrast, healthy sites showed initial signs of bone marrow formation on day 30, and subsequently a significantly greater proportion of mature bone marrow formation on both days 60 and 90. Radiographs exhibited sclerotic changes adjoining apical endodontic lesions, with scanning electron microscopy showing collapsed Volkmann canals protruding from these regions in the diseased sites. Furthermore, periodontal ligament fibers exhibited a parallel orientation to the alveolar walls of the diseased sites, in contrast to a perpendicular arrangement in the healthy sites. Conclusions Within the limitations of this study, it appears that a history of periodontal and endodontic pathology may critically affect bone formation and maturation, leading to delayed and compromised extraction socket

  1. Canine Models of Duchenne Muscular Dystrophy and Their Use in Therapeutic Strategies

    Science.gov (United States)

    Kornegay, Joe N.; Bogan, Janet R.; Bogan, Daniel J.; Childers, Martin K.; Li, Juan; Nghiem, Peter; Detwiler, David A.; Larsen, C. Aaron; Grange, Robert W.; Bhavaraju-Sanka, Ratna K.; Tou, Sandra; Keene, Bruce P.; Howard, James F.; Wang, Jiahui; Fan, Zheng; Schatzberg, Scott J.; Styner, Martin A.; Flanigan, Kevin M.; Xiao, Xiao; Hoffman, Eric P.

    2013-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder in which the loss of dystrophin causes progressive degeneration of skeletal and cardiac muscle. Potential therapies that carry substantial risk, such as gene and cell-based approaches, must first be tested in animal models, notably the mdx mouse and several dystrophin-deficient breeds of dogs, including golden retriever muscular dystrophy (GRMD). Affected dogs have a more severe phenotype, in keeping with that of DMD, so may better predict disease pathogenesis and treatment efficacy. We and others have developed various phenotypic tests to characterize disease progression in the GRMD model. These biomarkers range from measures of strength and joint contractures to magnetic resonance imaging. Some of these tests are routinely used in clinical veterinary practice, while others require specialized equipment and expertise. By comparing serial measurements from treated and untreated groups, one can document improvement or delayed progression of disease. Potential treatments for DMD may be broadly categorized as molecular, cellular, or pharmacologic. The GRMD model has increasingly been used to assess efficacy of a range of these therapies. While some of these studies have largely provided general proof-of-concept for the treatment under study, others have demonstrated efficacy using the biomarkers discussed. Importantly, just as symptoms in DMD vary among patients, GRMD dogs display remarkable phenotypic variation. While confounding statistical analysis in preclinical trials, this variation offers insight regarding the role that modifier genes play in disease pathogenesis. By correlating functional and mRNA profiling results, gene targets for therapy development can be identified. PMID:22218699

  2. Identification of canine coronary resistance and intramyocardial compliance on the basis of the waterfall model.

    Science.gov (United States)

    Burattini, R; Sipkema, P; van Huis, G A; Westerhof, N

    1985-01-01

    This study was performed to elucidate the effects of cardiac contraction on coronary pressure-flow relations. On the basis of the waterfall mechanism, a lumped model of the coronary arterial system is presented consisting of a proximal (epicardial) compliance, a coronary resistance, and an intramyocardial compliance. A "back"-pressure, assumed to be proportional (constant k) to left ventricular pressure, impedes flow. From steady-state measurements of circumflex coronary artery flow and inflow pressure, together with left ventricular pressure, the values of the three model parameters and the constant k have been estimated. In the control condition proximal compliance is found to be 1.7 X 10(-12) m4s2kg-1, intramyocardial compliance 110 X 10(-12)m4s2kg-1, and resistance 7.5 X 10(9) kgm-4s-1. The proportionality constant k is close to unity. Effects of changes in left ventricular pressure and inflow pressure and the effect of vasoactive drugs on the parameters are also investigated. Changes in coronary resistance are always opposite to changes in intramyocardial compliance. Sensitivity analysis showed that epicardial compliance plays its major role during isovolumic contraction and relaxation; resistance plays a role throughout the cardiac cycle but is more important in diastole than in systole, whereas intramyocardial compliance plays a role in systole and in early diastole.

  3. Effect of dasatinib in a xenograft mouse model of canine histiocytic sarcoma and in vitro expression status of its potential target EPHA2.

    Science.gov (United States)

    Ito, K; Miyamoto, R; Tani, H; Kurita, S; Kobayashi, M; Tamura, K; Bonkobara, M

    2018-02-01

    Canine histiocytic sarcoma (HS) is an aggressive and highly metastatic tumor. Previously, the kinase inhibitor dasatinib was shown to have potent growth inhibitory activity against HS cells in vitro, possibly via targeting the EPHA2 receptor. Here, the in vivo effect of dasatinib in HS cells was investigated using a xenograft mouse model. Moreover, the expression status of EPHA2 was examined in six HS cell lines, ranging from insensitive to highly sensitive to dasatinib. In the HS xenograft mouse model, dasatinib significantly suppressed tumor growth, as illustrated by a decrease in mitotic and Ki67 indices and an increase in apoptotic index in tumor tissues. On Western blot analysis, EPHA2 was only weakly detected in all HS cell lines, regardless of sensitivity to dasatinib. Dasatinib likely results in the inhibition of xenograft tumor growth via a mechanism other than targeting EPHA2. The findings of this study suggest that dasatinib is a targeted therapy drug worthy of further exploration for the treatment of canine HS. © 2017 John Wiley & Sons Ltd.

  4. A novel, ring-connected stent versus conventional GI stents: comparative study of physical properties and migration rates in a canine colon obstruction model.

    Science.gov (United States)

    Park, Hong Suk; Choo, In Wook; Seo, Soowon; Hyun, Dongho; Lim, Sooyoun; Kim, Jae J; Hong, Saet-Byul; Min, Byung-Hoon; Do, Young Soo; Choo, Sung Wook; Shin, Sung Wook; Park, Kwang Bo; Cho, Sung Ki

    2015-01-01

    Migration of stents is one of the most common adverse events in covered stent placement in GI tract obstruction. To compare physical property and migration rates in a canine colon obstruction model among a novel stent and conventional stents. Comparative physical test and animal study. Medical device testing laboratory and animal laboratory. Mongrel dogs (N=26). Surgical colon obstruction followed by placement of a novel (n=13) or conventional (n=13) stent. Physical properties, migration, and adverse events. The novel stent showed better flexibility, as in a physical test of longitudinal compressibility and axial force, than did conventional stents, and it withstood the fatigue test for 10 days. In terms of radial force and tensile strength, the novel stent showed the same or better results than conventional stents. In a canine colon obstruction model, the migration rate of a novel stent was significantly lower than that of a conventional stent (2/13, 15.4% vs 8/13, 61.5%; P=.008). Animal study of limited size. The novel, ring-connected stent is more flexible and more resistant to migration than the conventional stents. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  5. EW-7197 eluting nano-fiber covered self-expandable metallic stent to prevent granulation tissue formation in a canine urethral model.

    Directory of Open Access Journals (Sweden)

    Kichang Han

    Full Text Available To evaluate an EW-7197-eluting nanofiber-covered stent (NFCS for suppressing granulation tissue formation after stent placement in a canine urethral model.All experiments were approved by the committee of animal research. A total of 12 NFCSs were placed in the proximal and distal urethras of six dogs. Dogs were divided into two groups with 3 dogs each. The control stent (CS group received NFCSs and the drug stent (DS group received EW-7197 (1000 μg-eluting NFCSs. All dogs were sacrificed 8 weeks after stent placement Histologic findings of the stented urethra were compared using the Mann-Whitney U test.Stent placement was technically successful in all dogs without procedure-related complications. On urethrographic analysis, the mean luminal diameter was significantly larger in the DS group than in the CS group at 4 and 8 weeks after stent placement (all p 0.05.The EW-7197-eluting NFCS is effective and safe for suppressing granulation tissue formation after stent placement in a canine urethral model.

  6. Structural and in vivo mechanical characterization of canine patellar cartilage: a closed chondromalacia patellae model.

    Science.gov (United States)

    LaBerge, M; Audet, J; Drouin, G; Rivard, C H

    1993-01-01

    The purpose of this project was to study the relationship between the structure of the patellar cartilage and its response to static compressive loading with a closed chondromalacia patellae model. An animal model was used to induce degeneration of the patella that was monitored quantitatively and qualitatively as a function of time. Ten adult mongrel dogs had their left patellofemoral groove replaced by a customized metallic implant covered with a thin film of polyethylene for periods of 3 months (five dogs) and 6 months (five dogs). An indenter was designed to perform mechanical indentation testing on the patellar cartilage in situ. The animals were anesthetized and the response of patellar cartilage to a static compressive load of 4.5 MPa was monitored for 20 min and its relaxation after load removal for 20 min. Indentation tests were performed every 3 months of the implantation period. At the end of the implantation period, the patellae were processed for histology, and sections were stained with Safranin-O indicative of the proteoglycans content. Macroscopically, no apparent degeneration or fibrillation of the patellar surfaces was observed after 3 or 6 months of implantation. However, the patellar surface showed a change in coloration after 6 months. A 17 +/- 3% and 37 +/- 8% deformation of the cartilage were calculated for the 3-month and 6-month specimens, respectively. Histologically, a progressive loss of proteoglycans was observed in the matrix as a function of implantation time. These results indicated that an increase in cartilage compliance is associated with an intrinsic remodeling of the cartilage matrix and that these changes might occur without external signs of degeneration and can be quantified.

  7. Characterization of a canine model of glycogen storage disease type IIIa

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    Haiqing Yi

    2012-11-01

    Glycogen storage disease type IIIa (GSD IIIa is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously, a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR. The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT, aspartate transaminase (AST and alkaline phosphatase (ALP activities; serum creatine phosphokinase (CPK activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12 and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.

  8. Experimental models for Murray’s law

    Science.gov (United States)

    Akita, Dai; Kunita, Itsuki; Fricker, Mark D.; Kuroda, Shigeru; Sato, Katsuhiko; Nakagaki, Toshiyuki

    2017-01-01

    Transport networks are ubiquitous in multicellular organisms and include leaf veins, fungal mycelia and blood vessels. While transport of materials and signals through the network plays a crucial role in maintaining the living system, the transport capacity of the network can best be understood in terms of hydrodynamics. We report here that plasmodium from the large, single-celled amoeboid Physarum was able to construct a hydrodynamically optimized vein-network when evacuating biomass from confined arenas of various shapes through a narrow exit. Increasingly thick veins developed towards the exit, and the network spanned the arena via repetitive bifurcations to give a branching tree. The Hausdorff distance from all parts of the plasmodium to the vein network was kept low, whilst the hydrodynamic conductivity from distal parts of the network to the exit was equivalent, irrespective of the arena shape. This combination of spatial patterning and differential vein thickening served to evacuate biomass at an equivalent rate across the entire arena. The scaling relationship at the vein branches was determined experimentally to be 2.53-3.29, consistent with predictions from Murray’s law. Furthermore, we show that mathematical models for self-organised, adaptive transport in Physarum simulate the experimental network organisation well if the scaling coefficient of the current-reinforcement rule is set to 3. In simulations, this resulted in rapid development of an optimal network that minimised the combined volume and frictional energy in comparison with other scaling coefficients. This would predict that the boundary shear forces within each vein are constant throughout the network, and would be consistent with a feedback mechanism based on a sensing a threshold shear at the vein wall.

  9. Experimental models for Murray’s law

    International Nuclear Information System (INIS)

    Akita, Dai; Kunita, Itsuki; Fricker, Mark D; Kuroda, Shigeru; Sato, Katsuhiko; Nakagaki, Toshiyuki

    2017-01-01

    Transport networks are ubiquitous in multicellular organisms and include leaf veins, fungal mycelia and blood vessels. While transport of materials and signals through the network plays a crucial role in maintaining the living system, the transport capacity of the network can best be understood in terms of hydrodynamics. We report here that plasmodium from the large, single-celled amoeboid Physarum was able to construct a hydrodynamically optimized vein-network when evacuating biomass from confined arenas of various shapes through a narrow exit. Increasingly thick veins developed towards the exit, and the network spanned the arena via repetitive bifurcations to give a branching tree. The Hausdorff distance from all parts of the plasmodium to the vein network was kept low, whilst the hydrodynamic conductivity from distal parts of the network to the exit was equivalent, irrespective of the arena shape. This combination of spatial patterning and differential vein thickening served to evacuate biomass at an equivalent rate across the entire arena. The scaling relationship at the vein branches was determined experimentally to be 2.53–3.29, consistent with predictions from Murray’s law. Furthermore, we show that mathematical models for self-organised, adaptive transport in Physarum simulate the experimental network organisation well if the scaling coefficient of the current-reinforcement rule is set to 3. In simulations, this resulted in rapid development of an optimal network that minimised the combined volume and frictional energy in comparison with other scaling coefficients. This would predict that the boundary shear forces within each vein are constant throughout the network, and would be consistent with a feedback mechanism based on a sensing a threshold shear at the vein wall. (paper)

  10. Influence of Overt Diabetes Mellitus on Cyclosporine Pharmacokinetics in a Canine Model

    Directory of Open Access Journals (Sweden)

    Khalid M. Alkharfy

    2009-01-01

    Full Text Available Background/Aims. Diabetic patients usually require more medications than their nondiabetic counterparts. This work examined the effect of hyperglycemia on the pharmacokinetic properties of cyclosporine in a diabetic dog model. Main Methods. Diabetes was induced using a streptozotocin/alloxan combination and verified by measuring the serum glucose level. Cyclosporine was administered as a bolus intravenous dose of 5 mg/kg, and blood samples were collected at different time points for determining drug concentrations and biochemical analyses. Results. Diabetic dogs showed a significant increase in total body clearance of cyclosporine compared to healthy controls (0.457 L hr−1Kg−1 versus 0.201 L hr−1Kg−1, =.0019 and a decrease in its biological half-life (9.32 hours versus 22.56 hours, =.0125. In addition, diabetic animals exhibited a higher total cholesterol (7.20±0.62 mmol/L and 5.28±0.36 mmol/L; <.05 as well as more serum low density lipoproteins (4.45±0.72 mmol/L versus 1.06±0.10 mmol/L; <.05. Conclusion. Overt diabetes alters cyclosporine disposition by modulating its clearance. Abnormalities in the lipid profile, among other factors, may contribute to the accelerated metabolic degradation of cyclosporine under hyperglycemic conditions.

  11. Acute Management of Anterior Cruciate Ligament Injuries Using Novel Canine Models.

    Science.gov (United States)

    Bozynski, Chantelle C; Stannard, James P; Smith, Pat; Hanypsiak, Bryan T; Kuroki, Keiichi; Stoker, Aaron; Cook, Cristi; Cook, James L

    2016-10-01

    The objective of this study was to compare treatment options for acute management of anterior cruciate ligament (ACL) injuries using preclinical models. Twenty-seven adult purpose-bred research hounds underwent knee surgery (sham control, exposed ACL, or partial-tear ACL) and were assessed over the following 8 weeks. Dogs were randomized into three treatment groups: standard of care (i.e., rest and nonsteroidal anti-inflammatory drugs [NSAIDs]), washout, or leukoreduced platelet-rich plasma (PRP) so that a total of nine dogs received each treatment. Data from the two ACL-injury groups were pooled for each treatment ( n  = 6 per treatment group) and analyzed for treatment effects. The washout and PRP groups experienced less lameness, pain, and effusion, and greater function and comfortable range of motion compared with the NSAID group, with the PRP group showing most benefits. PRP was associated with the lowest severity of ACL pathology based on arthroscopic assessment. Measurable levels of inflammatory and degradative biomarkers were present in synovial fluid with significant differences noted over time. Based on these findings, washout had positive clinical effects compared with the standard-of-care group especially within the first week of treatment, but became less beneficial over time. A single injection of leukoreduced PRP was associated with favorable clinical results. However, no treatment was significantly "protective" against progression toward osteoarthritis after ACL injury. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  12. Evaluation of tumor motion effect in canine model for diagnostic and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sangkeun; Nam, Taewon; Kim, Kyeongmin [Molecular Imaging Research Center, Seoul (Korea, Republic of); Park, Seungwoo; Han, Suchul; Ji, Younghoon [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Park, Nohwon; Eom, Kidong [Konkuk Univ., Seoul (Korea, Republic of)

    2013-05-15

    The internal organs move up to 35mm maximum and it provides information and uncertainty that has been distorted in the diagnosis and treatment. Previous most studies for the effect of respiration have been performed with external monitoring systems but it cannot represent internal organ motion such as liver, pancreas, and lung. Positron emission tomography (PET) is more influenced by motion than computed tomography (CT) and magnetic resonance imaging (MRI) since measurement time for image acquisition is longer than CT and MRI. Thus, count of tumor is to be underestimated and region of tumor is to be overestimated. The first aim of this study was developing the artificial pulmonary nodule which can be performed non-invasive transplant into thorax of dogs and second is to assess the effect of respiratory motion on PET image with evaluating the applicability of the artificial model using dogs for diagnosis and treatment. The developed artificial pulmonary nodule showed reproducibility and motion effect as respiratory cycle and it was verified in PET images. Radiation dose estimated was not changed and was reduced slightly of 10 rpm and 15 rpm, respectively, in both of glass dosimeter and ion chamber. The developed artificial pulmonary nodule will be useful tool for evaluating respiratory motion and better research performance for diagnosis and treatment will be expected with performing simulated experiment using the nodule conducted in this study.

  13. Efficacy of a laparoscopic gastric restrictive device in an obese canine model.

    Science.gov (United States)

    Guo, Xiaomei; Mattar, Samer G; Mimms, Scott E; Navia, Jose A; Kassab, Ghassan S

    2014-01-01

    Bariatric surgery using laparoscopic techniques is the most effective treatment for morbid obesity. The objective of the study is to assess the safety and efficacy of a novel laparoscopic reversible gastric restrictive (RGR) device in a group of obese dogs. An implant was also performed in a cadaver to assess implant feasibility in a human. Four obese mongrel dogs were subjected to RGR implantation for 3 months followed by recovery for an additional 6 weeks after device removal. Food intake, body weight, radiographic barium imaging, and gastric endoscopy were used to monitor RGR performance before implant, after implant, and implant removal. An additional RGR laparoscopic implantation procedure was performed in a human cadaver. The implanted obese dogs exhibited a significant decrease in food intake and body weight over 3 months with the RGR device. The reduction of food intake was sustained at an average of 46 % after implant and the excess weight loss reached an average of 75 % at the end of 12 weeks with recovery to approximately 78 % of baseline after 6 weeks of implant removal. Barium imaging and gastric endoscopy both confirmed passage for food through the restrictive device channel in the stomach. The RGR device was successfully implanted laparoscopically on the cadaver stomach in less than an hour. The RGR device is laparoscopically deliverable and removable with effective and sustainable weight loss over a 12-week period in an obese dog model. The implant is also technically feasible in man.

  14. Clinical toxicity of peripheral nerve to intraoperative radiotherapy in a canine model

    International Nuclear Information System (INIS)

    Johnstone, Peter A. S.; DeLuca, Anne Marie; Bacher, John D.; Hampshire, Victoria A.; Terrill, Richard E.; Anderson, William J.; Kinsella, Timothy J.; Sindelar, William F.

    1995-01-01

    Purpose: The clinical late effects of intraoperative radiotherapy (IORT) on peripheral nerve were investigated in a foxhound model. Methods and Materials: Between 1982 and 1987, 40 animals underwent laparotomy with intraoperative radiotherapy of doses from 0-75 Gy administered to the right lumbosacral plexus. Subsequently, all animals were monitored closely and sacrificed to assess clinical effects to peripheral nerve. This analysis reports final clinical results of all animals, with follow-up to 5 years. Results: All animals treated with ≥ 25 Gy developed ipsilateral neuropathy. An inverse relationship was noted between intraoperative radiotherapy dose and time to neuropathy, with an effective dose for 50% paralysis (ED 50 ) of 17.2 Gy. One of the animals treated with 15 Gy IORT developed paralysis, after a much longer latency than the other animals. Conclusions: Doses of 15 Gy delivered intraoperatively may be accompanied by peripheral neuropathy with long-term follow-up. This threshold is less than that reported with shorter follow-up. The value of ED 50 determined here is in keeping with data from other animal trials, and from clinical trials in humans

  15. Diaphragm remodeling and compensatory respiratory mechanics in a canine model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Mead, A F; Petrov, M; Malik, A S; Mitchell, M A; Childers, M K; Bogan, J R; Seidner, G; Kornegay, J N; Stedman, H H

    2014-04-01

    Ventilatory insufficiency remains the leading cause of death and late stage morbidity in Duchenne muscular dystrophy (DMD). To address critical gaps in our knowledge of the pathobiology of respiratory functional decline, we used an integrative approach to study respiratory mechanics in a translational model of DMD. In studies of individual dogs with the Golden Retriever muscular dystrophy (GRMD) mutation, we found evidence of rapidly progressive loss of ventilatory capacity in association with dramatic morphometric remodeling of the diaphragm. Within the first year of life, the mechanics of breathing at rest, and especially during pharmacological stimulation of respiratory control pathways in the carotid bodies, shift such that the primary role of the diaphragm becomes the passive elastic storage of energy transferred from abdominal wall muscles, thereby permitting the expiratory musculature to share in the generation of inspiratory pressure and flow. In the diaphragm, this physiological shift is associated with the loss of sarcomeres in series (∼ 60%) and an increase in muscle stiffness (∼ 900%) compared with those of the nondystrophic diaphragm, as studied during perfusion ex vivo. In addition to providing much needed endpoint measures for assessing the efficacy of therapeutics, we expect these findings to be a starting point for a more precise understanding of respiratory failure in DMD.

  16. Finite element analysis of rapid canine retraction through reducing resistance and distraction

    Directory of Open Access Journals (Sweden)

    Junjie XUE

    2014-01-01

    Full Text Available Objective: The aims of this study were to compare different surgical approaches to rapid canine retraction by designing and selecting the most effective method of reducing resistance by a three-dimensional finite element analysis. Material and Methods: Three-dimensional finite element models of different approaches to rapid canine retraction by reducing resistance and distraction were established, including maxillary teeth, periodontal ligament, and alveolar. The models were designed to dissect the periodontal ligament, root, and alveolar separately. A 1.5 N force vector was loaded bilaterally to the center of the crown between first molar and canine, to retract the canine distally. The value of total deformation was used to assess the initial displacement of the canine and molar at the beginning of force loading. Stress intensity and force distribution were analyzed and evaluated by Ansys 13.0 through comparison of equivalent (von Mises stress and maximum shear stress. Results: The maximum value of total deformation with the three kinds of models occurred in the distal part of the canine crown and gradually reduced from the crown to the apex of the canine; compared with the canines in model 3 and model 1, the canine in model 2 had the maximum value of displacement, up to 1.9812 mm. The lowest equivalent (von Mises stress and the lowest maximum shear stress were concentrated mainly on the distal side of the canine root in model 2. The distribution of equivalent (von Mises stress and maximum shear stress on the PDL of the canine in the three models was highly concentrated on the distal edge of the canine cervix. . Conclusions: Removal of the bone in the pathway of canine retraction results in low stress intensity for canine movement. Periodontal distraction aided by surgical undermining of the interseptal bone would reduce resistance and effectively accelerate the speed of canine retraction.

  17. Contribution of Schwann Cells to Remyelination in a Naturally Occurring Canine Model of CNS Neuroinflammation.

    Directory of Open Access Journals (Sweden)

    Kristel Kegler

    Full Text Available Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide evidence for regeneration promoting cells recruitable for therapeutic purposes. There is evidence that neurotrophin receptor p75 (p75NTR-expressing cells emerge in the lesioned CNS. However, the phenotype and identity of these cells, and signals triggering their in situ generation under normal conditions and certain pathological situations has remained enigmatic. In the present study, we used a spontaneous, idiopathic and inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration as a model to study the phenotype of Schwann cells and their relation to Schwann cell remyelination within the CNS. Furthermore, the phenotype of p75NTR-expressing cells within the injured CNS was compared to their counter-part in control sciatic nerve and after peripheral nerve injury. In addition, organotypic slice cultures were used to further elucidate the origin of p75NTR-positive cells. In cerebral and cerebellar white and grey matter lesions as well as in the brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-α. Interestingly, and contrary to the findings in control sciatic nerves, p75NTR-expressing cells only co-localized with Sox2 in degenerative neuropathy, thus suggesting that such cells might represent dedifferentiated Schwann cells both in the injured CNS and PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and P0-positive mature myelinating Schwann cells, was strikingly associated with the presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage-dominated inflammatory response provided an adequate environment for Schwann cells plasticity within the injured CNS. Furthermore, axonal damage was reduced in brain stem areas

  18. Receptor for advanced glycation end products involved in lung ischemia reperfusion injury in cardiopulmonary bypass attenuated by controlled oxygen reperfusion in a canine model.

    Science.gov (United States)

    Rong, Jian; Ye, Sheng; Liang, Meng-ya; Chen, Guang-xian; Liu, Hai; Zhang, Jin-Xin; Wu, Zhong-kai

    2013-01-01

    Controlled oxygen reperfusion could protect the lung against ischemia-reperfusion injury in cardiopulmonary bypass (CPB) by downregulating high mobility group box 1 (HMGB1), a high affinity receptor of HMGB1. This study investigated the effect of controlled oxygen reperfusion on receptor for advanced glycation end products (RAGE) expression and its downstream effects on lung ischemia-reperfusion injury. Fourteen canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest followed by 90 minutes of reperfusion. Animals were randomized to receive 80% FiO2 during the entire procedure (control group) or to a test group receiving a controlled oxygen reperfusion protocol. Pathologic changes in lung tissues, RAGE expression, serum interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated. The lung pathologic scores after 25 and 90 minutes of reperfusion were significantly lower in the test group compared with the control group (p RAGE expression, TNF-α, and IL-6 were downregulated by controlled oxygen treatment (p RAGE might be involved in the lung ischemia-reperfusion injury in canine model of CPB, which was downregulated by controlled oxygen reperfusion.

  19. Effects of low-energy laser irradiation on the distalization velocity during experimental canine tooth movement in humans: 'comparative clinical study'

    International Nuclear Information System (INIS)

    Cruz, Delma Rebelo

    2003-01-01

    This research investigated the effects of low level laser therapy (LLLT) upon the velocity of canine tooth movement and consequently bone remodeling. A total of eleven patients were treated with a 780 nm diode laser. One side of the upper arcade was considered control group and was not irradiated but received mechanical activation every thirty days. The opposite side received the same mechanical activation but was also irradiated at days 0, 3, 7 and 14 of each month. Data of the biometrical progress were taken on both sides on days 3,7,14,21 and 30 of each month. The results indicate that all patients showed significant acceleration of the distalization velocity on the side treated with LLLT when compared to the control. (author)

  20. Standard Model theory calculations and experimental tests

    International Nuclear Information System (INIS)

    Cacciari, M.; Hamel de Monchenault, G.

    2015-01-01

    To present knowledge, all the physics at the Large Hadron Collider (LHC) can be described in the framework of the Standard Model (SM) of particle physics. Indeed the newly discovered Higgs boson with a mass close to 125 GeV seems to confirm the predictions of the SM. Thus, besides looking for direct manifestations of the physics beyond the SM, one of the primary missions of the LHC is to perform ever more stringent tests of the SM. This requires not only improved theoretical developments to produce testable predictions and provide experiments with reliable event generators, but also sophisticated analyses techniques to overcome the formidable experimental environment of the LHC and perform precision measurements. In the first section, we describe the state of the art of the theoretical tools and event generators that are used to provide predictions for the production cross sections of the processes of interest. In section 2, inclusive cross section measurements with jets, leptons and vector bosons are presented. Examples of differential cross sections, charge asymmetries and the study of lepton pairs are proposed in section 3. Finally, in section 4, we report studies on the multiple production of gauge bosons and constraints on anomalous gauge couplings

  1. IVIM: modeling, experimental validation and application to animal models

    International Nuclear Information System (INIS)

    Fournet, Gabrielle

    2016-01-01

    This PhD thesis is centered on the study of the IVIM ('Intravoxel Incoherent Motion') MRI sequence. This sequence allows for the study of the blood microvasculature such as the capillaries, arterioles and venules. To be sensitive only to moving groups of spins, diffusion gradients are added before and after the 180 degrees pulse of a spin echo (SE) sequence. The signal component corresponding to spins diffusing in the tissue can be separated from the one related to spins travelling in the blood vessels which is called the IVIM signal. These two components are weighted by f IVIM which represents the volume fraction of blood inside the tissue. The IVIM signal is usually modelled by a mono-exponential (ME) function and characterized by a pseudo-diffusion coefficient, D*. We propose instead a bi-exponential IVIM model consisting of a slow pool, characterized by F slow and D* slow corresponding to the capillaries as in the ME model, and a fast pool, characterized by F fast and D* fast, related to larger vessels such as medium-size arterioles and venules. This model was validated experimentally and more information was retrieved by comparing the experimental signals to a dictionary of simulated IVIM signals. The influence of the pulse sequence, the repetition time and the diffusion encoding time was also studied. Finally, the IVIM sequence was applied to the study of an animal model of Alzheimer's disease. (author) [fr

  2. Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model.

    Science.gov (United States)

    Lange, Sandra; Steder, Anne; Glass, Änne; Killian, Doreen; Wittmann, Susanne; Machka, Christoph; Werner, Juliane; Schäfer, Stephanie; Roolf, Catrin; Junghanss, Christian

    2016-04-01

    The canine hematopoietic stem cell transplantation (HSCT) model has become accepted in recent decades as a good preclinical model for the development of new transplantation strategies. Information on factors associated with outcome after allogeneic HSCT are a prerequisite for designing new risk-adapted transplantation protocols. Here we report a retrospective analysis aimed at identifying risk factors for allograft rejection in the canine HSCT model. A total of 75 dog leukocyte antigen-identical sibling HSCTs were performed since 2003 on 10 different protocols. Conditioning consisted of total body irradiation at 1.0 Gy (n = 20), 2.0 Gy (n = 40), or 4.5 Gy (n = 15). Bone marrow was infused either intravenously (n = 54) or intraosseously (n = 21). Cyclosporin A alone or different combinations of cyclosporine A, mycophenolate mofetil, and everolimus were used for immunosuppression. A median cell dose of 3.5 (range, 1.0 to 11.8) total nucleated cells (TNCs)/kg was infused. Cox analyses were used to assess the influence of age, weight, radiation dose, donor/recipient sex, type of immunosuppression, and cell dose (TNCs, CD34(+) cells) on allograft rejection. Initial engraftment occurred in all dogs. Forty-two dogs (56%) experienced graft rejection at median of 11 weeks (range, 6 to 56 weeks) after HSCT. Univariate analyses revealed radiation dose, type of immunosuppression, TNC dose, recipient weight, and recipient age as factors influencing long-term engraftment. In multivariate analysis, low radiation dose (P rejection. Peripheral blood mononuclear cell chimerism ≥30% (P = .008) and granulocyte chimerism ≥70% (P = .023) at 4 weeks after HSCT were independent predictors of stable engraftment. In summary, these data indicate that even in low-dose total body irradiation-based regimens, the irradiation dose is important for engraftment. The level of blood chimerism at 4 weeks post-HSCT was predictive of long-term engraftment in the canine HSCT

  3. Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model.

    Science.gov (United States)

    Willems, Nicole; Yang, Hsiao-Yin; Langelaan, Marloes L P; Tellegen, Anna R; Grinwis, Guy C M; Kranenburg, Hendrik-Jan C; Riemers, Frank M; Plomp, Saskia G M; Craenmehr, Eric G M; Dhert, Wouter J A; Papen-Botterhuis, Nicole E; Meij, Björn P; Creemers, Laura B; Tryfonidou, Marianna A

    2015-08-20

    Chronic low back pain due to intervertebral disc (IVD) degeneration is associated with increased levels of inflammatory mediators. Current medical treatment consists of oral anti-inflammatory drugs to alleviate pain. In this study, the efficacy and safety of a novel thermoreversible poly-N-isopropylacrylamide MgFe-layered double hydroxide (pNIPAAM MgFe-LDH) hydrogel was evaluated for intradiscal controlled delivery of the selective cyclooxygenase (COX) 2 inhibitor and anti-inflammatory drug celecoxib (CXB). Degradation, release behavior, and the ability of a CXB-loaded pNIPAAM MgFe-LDH hydrogel to suppress prostaglandin E2 (PGE2) levels in a controlled manner in the presence of a proinflammatory stimulus (TNF-α) were evaluated in vitro. Biocompatibility was evaluated histologically after subcutaneous injection in mice. Safety of intradiscal application of the loaded and unloaded hydrogels was studied in a canine model of spontaneous mild IVD degeneration by histological, biomolecular, and biochemical evaluation. After the hydrogel was shown to be biocompatible and safe, an in vivo dose-response study was performed in order to determine safety and efficacy of the pNIPAAM MgFe-LDH hydrogel for intradiscal controlled delivery of CXB. CXB release correlated to hydrogel degradation in vitro. Furthermore, controlled release from CXB-loaded hydrogels was demonstrated to suppress PGE2 levels in the presence of TNF-α. The hydrogel was shown to exhibit a good biocompatibility upon subcutaneous injection in mice. Upon intradiscal injection in a canine model, the hydrogel exhibited excellent biocompatibility based on histological evaluation of the treated IVDs. Gene expression and biochemical analyses supported the finding that no substantial negative effects of the hydrogel were observed. Safety of application was further confirmed by the absence of clinical symptoms, IVD herniation or progression of degeneration. Controlled release of CXB resulted in a nonsignificant

  4. Biomass thermochemical gasification: Experimental studies and modeling

    Science.gov (United States)

    Kumar, Ajay

    The overall goals of this research were to study the biomass thermochemical gasification using experimental and modeling techniques, and to evaluate the cost of industrial gas production and combined heat and power generation. This dissertation includes an extensive review of progresses in biomass thermochemical gasification. Product gases from biomass gasification can be converted to biopower, biofuels and chemicals. However, for its viable commercial applications, the study summarizes the technical challenges in the gasification and downstream processing of product gas. Corn stover and dried distillers grains with solubles (DDGS), a non-fermentable byproduct of ethanol production, were used as the biomass feedstocks. One of the objectives was to determine selected physical and chemical properties of corn stover related to thermochemical conversion. The parameters of the reaction kinetics for weight loss were obtained. The next objective was to investigate the effects of temperature, steam to biomass ratio and equivalence ratio on gas composition and efficiencies. DDGS gasification was performed on a lab-scale fluidized-bed gasifier with steam and air as fluidizing and oxidizing agents. Increasing the temperature resulted in increases in hydrogen and methane contents and efficiencies. A model was developed to simulate the performance of a lab-scale gasifier using Aspen Plus(TM) software. Mass balance, energy balance and minimization of Gibbs free energy were applied for the gasification to determine the product gas composition. The final objective was to optimize the process by maximizing the net energy efficiency, and to estimate the cost of industrial gas, and combined heat and power (CHP) at a biomass feedrate of 2000 kg/h. The selling price of gas was estimated to be 11.49/GJ for corn stover, and 13.08/GJ for DDGS. For CHP generation, the electrical and net efficiencies were 37 and 86%, respectively for corn stover, and 34 and 78%, respectively for DDGS. For

  5. Biomechanics of an orthosis-managed cranial cruciate ligament-deficient canine stifle joint predicted by use of a computer model.

    Science.gov (United States)

    Bertocci, Gina E; Brown, Nathan P; Mich, Patrice M

    2017-01-01

    OBJECTIVE To evaluate effects of an orthosis on biomechanics of a cranial cruciate ligament (CrCL)-deficient canine stifle joint by use of a 3-D quasistatic rigid-body pelvic limb computer model simulating the stance phase of gait and to investigate influences of orthosis hinge stiffness (durometer). SAMPLE A previously developed computer simulation model for a healthy 33-kg 5-year-old neutered Golden Retriever. PROCEDURES A custom stifle joint orthosis was implemented in the CrCL-deficient pelvic limb computer simulation model. Ligament loads, relative tibial translation, and relative tibial rotation in the orthosis-stabilized stifle joint (baseline scenario; high-durometer hinge]) were determined and compared with values for CrCL-intact and CrCL-deficient stifle joints. Sensitivity analysis was conducted to evaluate the influence of orthosis hinge stiffness on model outcome measures. RESULTS The orthosis decreased loads placed on the caudal cruciate and lateral collateral ligaments and increased load placed on the medial collateral ligament, compared with loads for the CrCL-intact stifle joint. Ligament loads were decreased in the orthosis-managed CrCL-deficient stifle joint, compared with loads for the CrCL-deficient stifle joint. Relative tibial translation and rotation decreased but were not eliminated after orthosis management. Increased orthosis hinge stiffness reduced tibial translation and rotation, whereas decreased hinge stiffness increased internal tibial rotation, compared with values for the baseline scenario. CONCLUSIONS AND CLINICAL RELEVANCE Stifle joint biomechanics were improved following orthosis implementation, compared with biomechanics of the CrCL-deficient stifle joint. Orthosis hinge stiffness influenced stifle joint biomechanics. An orthosis may be a viable option to stabilize a CrCL-deficient canine stifle joint.

  6. Injury Based on Its Study in Experimental Models

    Directory of Open Access Journals (Sweden)

    M. Mendes-Braz

    2012-01-01

    Full Text Available The present review focuses on the numerous experimental models used to study the complexity of hepatic ischemia/reperfusion (I/R injury. Although experimental models of hepatic I/R injury represent a compromise between the clinical reality and experimental simplification, the clinical transfer of experimental results is problematic because of anatomical and physiological differences and the inevitable simplification of experimental work. In this review, the strengths and limitations of the various models of hepatic I/R are discussed. Several strategies to protect the liver from I/R injury have been developed in animal models and, some of these, might find their way into clinical practice. We also attempt to highlight the fact that the mechanisms responsible for hepatic I/R injury depend on the experimental model used, and therefore the therapeutic strategies also differ according to the model used. Thus, the choice of model must therefore be adapted to the clinical question being answered.

  7. Prospects of experimentally reachable beyond Standard Model ...

    Indian Academy of Sciences (India)

    2016-01-06

    Jan 6, 2016 ... Since then, the theory has been experimentally verified to a ... Despite the fact that SM has unravelled the gauge origin of fundamental forces and the structure of Universe while successfully confronting numerous ...

  8. Upper canine inclination influences the aesthetics of a smile.

    Science.gov (United States)

    Bothung, C; Fischer, K; Schiffer, H; Springer, I; Wolfart, S

    2015-02-01

    This current study investigated which angle of canine inclination (angle between canine tooth axis (CA-line) and the line between the lateral canthus and the ipsilateral labial angle (EM-line)) is perceived to be most attractive in a smile. The second objective was to determine whether laymen and dental experts share the same opinion. A Q-sort assessment was performed with 48 posed smile photographs to obtain two models of neutral facial attractiveness. Two sets of images (1 male model set, 1 female model set), each containing seven images with incrementally altered canine and posterior teeth inclinations, were generated. The images were ranked for attractiveness by three groups (61 laymen, 59 orthodontists, 60 dentists). The images with 0° inclination, that is CA-line (maxillary canine axis) parallel to EM-line (the line formed by the lateral canthus and the ipsilateral corner of the mouth) (male model set: 54·4%; female model set: 38·9%), or -5° (inward) inclination (male model set: 20%; female model set: 29·4%) were perceived to be most attractive within each set. Images showing inward canine inclinations were regarded to be more attractive than those with outward inclinations. Dental experts and laymen were in accordance with the aesthetics. Smiles were perceived to be most attractive when the upper canine tooth axis was parallel to the EM-line. In reconstructive or orthodontic therapy, it is thus important to incline canines more inwardly than outwardly. © 2014 John Wiley & Sons Ltd.

  9. Collateral ventilation quantification using xenon-enhanced dynamic dual-energy CT: Differences between canine and swine models of bronchial occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ah; Goo, Jin Mo; Park, Sang Joon; Lee, Chang Hyun; Park, Chng Min [Dept. of Radiology, Seoul National University College of Medicine and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul (Korea, Republic of)

    2015-06-15

    The aim of this study was to evaluate whether the difference in the degree of collateral ventilation between canine and swine models of bronchial obstruction could be detected by using xenon-enhanced dynamic dual-energy CT. Eight mongrel dogs and six pigs underwent dynamic dual-energy scanning of 64-slice dual-source CT at 12-second interval for 2-minute wash-in period (60% xenon) and at 24-second interval for 3-minute wash-out period with segmental bronchus occluded. Ventilation parameters of magnitude (A value), maximal slope, velocity (K value), and time-to-peak (TTP) enhancement were calculated from dynamic xenon maps using exponential function of Kety model. A larger difference in A value between parenchyma was observed in pigs than in dogs (absolute difference, -33.0 +/- 5.0 Hounsfield units [HU] vs. -2.8 +/- 7.1 HU, p = 0.001; normalized percentage difference, -79.8 +/- 1.8% vs. -5.4 +/- 16.4%, p = 0.0007). Mean maximal slopes in both periods in the occluded parenchyma only decreased in pigs (all p < 0.05). K values of both periods were not different (p = 0.892) in dogs. However, a significant (p = 0.027) difference was found in pigs in the wash-in period. TTP was delayed in the occluded parenchyma in pigs (p = 0.013) but not in dogs (p = 0.892). Xenon-ventilation CT allows the quantification of collateral ventilation and detection of differences between canine and swine models of bronchial obstruction.

  10. Collateral ventilation quantification using xenon-enhanced dynamic dual-energy CT: Differences between canine and swine models of bronchial occlusion

    International Nuclear Information System (INIS)

    Kim, Eun Ah; Goo, Jin Mo; Park, Sang Joon; Lee, Chang Hyun; Park, Chng Min

    2015-01-01

    The aim of this study was to evaluate whether the difference in the degree of collateral ventilation between canine and swine models of bronchial obstruction could be detected by using xenon-enhanced dynamic dual-energy CT. Eight mongrel dogs and six pigs underwent dynamic dual-energy scanning of 64-slice dual-source CT at 12-second interval for 2-minute wash-in period (60% xenon) and at 24-second interval for 3-minute wash-out period with segmental bronchus occluded. Ventilation parameters of magnitude (A value), maximal slope, velocity (K value), and time-to-peak (TTP) enhancement were calculated from dynamic xenon maps using exponential function of Kety model. A larger difference in A value between parenchyma was observed in pigs than in dogs (absolute difference, -33.0 +/- 5.0 Hounsfield units [HU] vs. -2.8 +/- 7.1 HU, p = 0.001; normalized percentage difference, -79.8 +/- 1.8% vs. -5.4 +/- 16.4%, p = 0.0007). Mean maximal slopes in both periods in the occluded parenchyma only decreased in pigs (all p < 0.05). K values of both periods were not different (p = 0.892) in dogs. However, a significant (p = 0.027) difference was found in pigs in the wash-in period. TTP was delayed in the occluded parenchyma in pigs (p = 0.013) but not in dogs (p = 0.892). Xenon-ventilation CT allows the quantification of collateral ventilation and detection of differences between canine and swine models of bronchial obstruction.

  11. Intra-articular enzyme replacement therapy with rhIDUA is safe, well-tolerated, and reduces articular GAG storage in the canine model of mucopolysaccharidosis type I.

    Science.gov (United States)

    Wang, Raymond Y; Aminian, Afshin; McEntee, Michael F; Kan, Shih-Hsin; Simonaro, Calogera M; Lamanna, William C; Lawrence, Roger; Ellinwood, N Matthew; Guerra, Catalina; Le, Steven Q; Dickson, Patricia I; Esko, Jeffrey D

    2014-08-01

    Treatment with intravenous enzyme replacement therapy and hematopoietic stem cell transplantation for mucopolysaccharidosis (MPS) type I does not address joint disease, resulting in persistent orthopedic complications and impaired quality of life. A proof-of-concept study was conducted to determine the safety, tolerability, and efficacy of intra-articular recombinant human iduronidase (IA-rhIDUA) enzyme replacement therapy in the canine MPS I model. Four MPS I dogs underwent monthly rhIDUA injections (0.58 mg/joint) into the right elbow and knee for 6 months. Contralateral elbows and knees concurrently received normal saline. No intravenous rhIDUA therapy was administered. Monthly blood counts, chemistries, anti-rhIDUA antibody titers, and synovial fluid cell counts were measured. Lysosomal storage of synoviocytes and chondrocytes, synovial macrophages and plasma cells were scored at baseline and 1 month following the final injection. All injections were well-tolerated without adverse reactions. One animal required prednisone for spinal cord compression. There were no clinically significant abnormalities in blood counts or chemistries. Circulating anti-rhIDUA antibody titers gradually increased in all dogs except the prednisone-treated dog; plasma cells, which were absent in all baseline synovial specimens, were predominantly found in synovium of rhIDUA-treated joints at study-end. Lysosomal storage in synoviocytes and chondrocytes following 6 months of IA-rhIDUA demonstrated significant reduction compared to tissues at baseline, and saline-treated tissues at study-end. Mean joint synovial GAG levels in IA-rhIDUA joints were 8.62 ± 5.86 μg/mg dry weight and 21.6 ± 10.4 μg/mg dry weight in control joints (60% reduction). Cartilage heparan sulfate was also reduced in the IA-rhIDUA joints (113 ± 39.5 ng/g wet weight) compared to saline-treated joints (142 ± 56.4 ng/g wet weight). Synovial macrophage infiltration, which was present in all joints at baseline, was

  12. Canine oral melanoma.

    Science.gov (United States)

    Bergman, Philip J

    2007-05-01

    Melanoma is the most common oral malignancy in the dog. Oral and/or mucosal melanoma has been routinely considered an extremely malignant tumor with a high degree of local invasiveness and high metastatic propensity. Primary tumor size has been found to be extremely prognostic. The World Health Organization staging scheme for dogs with oral melanoma is based on size, with stage I = or = 4cm tumor and/or lymph node metastasis, and stage IV = distant metastasis. Median survival times for dogs with oral melanoma treated with surgery are approximately 17 to 18, 5 to 6, and 3 months with stage I, II, and III disease, respectively. Significant negative prognostic factors include stage, size, evidence of metastasis, and a variety of histologic criteria. Standardized treatments such as surgery, coarse-fractionation radiation therapy, and chemotherapy have afforded minimal to modest stage-dependent clinical benefits and death is usually due to systemic metastasis. Numerous immunotherapeutic strategies have been employed to date with limited clinical efficacy; however, the use of xenogeneic DNA vaccines may represent a leap forward in clinical efficacy. Oral melanoma is a spontaneous syngeneic cancer occurring in outbred, immunocompetent dogs and appears to be a more clinically faithful therapeutic model for human melanoma; further use of canine melanoma as a therapeutic model for human melanoma is strongly encouraged. In addition, the development of an expanded but clinically relevant staging system incorporating the aforementioned prognostic factors is also strongly encouraged.

  13. MREIT conductivity imaging of the postmortem canine abdomen using CoReHA

    International Nuclear Information System (INIS)

    Jeon, Kiwan; Lee, Chang-Ock; Minhas, Atul S; Kim, Young Tae; Jeong, Woo Chul; Kim, Hyung Joong; Woo, Eung Je; Kang, Byeong Teck; Park, Hee Myung; Seo, Jin Keun

    2009-01-01

    Magnetic resonance electrical impedance tomography (MREIT) is a new bio-imaging modality providing cross-sectional conductivity images from measurements of internal magnetic flux densities produced by externally injected currents. Recent experimental results of postmortem and in vivo imaging of the canine brain demonstrated its feasibility by showing conductivity images with meaningful contrast among different brain tissues. MREIT image reconstructions involve a series of data processing steps such as k-space data handling, phase unwrapping, image segmentation, meshing, modelling, finite element computation, denoising and so on. To facilitate experimental studies, we need a software tool that automates these data processing steps. In this paper, we summarize such an MREIT software package called CoReHA (conductivity reconstructor using harmonic algorithms). Performing imaging experiments of the postmortem canine abdomen, we demonstrate how CoReHA can be utilized in MREIT. The abdomen with a relatively large field of view and various organs imposes new technical challenges when it is chosen as an imaging domain. Summarizing a few improvements in the experimental MREIT technique, we report our first conductivity images of the postmortem canine abdomen. Illustrating reconstructed conductivity images, we discuss how they discern different organs including the kidney, spleen, stomach and small intestine. We elaborate, as an example, that conductivity images of the kidney show clear contrast among cortex, internal medulla, renal pelvis and urethra. We end this paper with a brief discussion on future work using different animal models

  14. A LINE-1 Insertion in DLX6 Is Responsible for Cleft Palate and Mandibular Abnormalities in a Canine Model of Pierre Robin Sequence

    Science.gov (United States)

    Wolf, Zena T.; Leslie, Elizabeth J.; Arzi, Boaz; Jayashankar, Kartika; Karmi, Nili; Jia, Zhonglin; Rowland, Douglas J.; Young, Amy; Safra, Noa; Sliskovic, Saundra; Murray, Jeffrey C.; Wade, Claire M.; Bannasch, Danika L.

    2014-01-01

    Cleft palate (CP) is one of the most commonly occurring craniofacial birth defects in humans. In order to study cleft palate in a naturally occurring model system, we utilized the Nova Scotia Duck Tolling Retriever (NSDTR) dog breed. Micro-computed tomography analysis of CP NSDTR craniofacial structures revealed that these dogs exhibit defects similar to those observed in a recognizable subgroup of humans with CP: Pierre Robin Sequence (PRS). We refer to this phenotype in NSDTRs as CP1. Individuals with PRS have a triad of birth defects: shortened mandible, posteriorly placed tongue, and cleft palate. A genome-wide association study in 14 CP NSDTRs and 72 unaffected NSDTRs identified a significantly associated region on canine chromosome 14 (24.2 Mb–29.3 Mb; praw = 4.64×10−15). Sequencing of two regional candidate homeobox genes in NSDTRs, distal-less homeobox 5 (DLX5) and distal-less homeobox 6 (DLX6), identified a 2.1 kb LINE-1 insertion within DLX6 in CP1 NSDTRs. The LINE-1 insertion is predicted to insert a premature stop codon within the homeodomain of DLX6. This prompted the sequencing of DLX5 and DLX6 in a human cohort with CP, where a missense mutation within the highly conserved DLX5 homeobox of a patient with PRS was identified. This suggests the involvement of DLX5 in the development of PRS. These results demonstrate the power of the canine animal model as a genetically tractable approach to understanding naturally occurring craniofacial birth defects in humans. PMID:24699068

  15. Vasodilative effects of prostaglandin E1 derivate on arteries of nerve roots in a canine model of a chronically compressed cauda equina

    Directory of Open Access Journals (Sweden)

    Konno Shin-ichi

    2008-04-01

    Full Text Available Abstract Background Reduction of blood flow is important in the induction of neurogenic intermittent claudication (NIC in lumbar spinal canal stenosis. PGE1 improves the mean walking distance in patients with NIC type cauda equina compression. PGE1 derivate might be effective in dilating blood vessels and improving blood flow in nerve roots with chronically compressed cauda equina. The aim of this study was to assess whether PGE1 derivate has vasodilatory effects on both arteries and veins in a canine model of chronic cauda equina compression. Methods Fourteen dogs were used in this study. A plastic balloon inflated to 10 mmHg was placed under the lamina of the 7th lumbar vertebra for 1 week. OP-1206-cyclodextrin clathrate (OP-1206-CD: prostaglandin E1 derivate was administered orally. The blood vessels of the second or third sacral nerve root were identified using a specially designed surgical microscope equipped with a video camera. The diameter of the blood vessels was measured on video-recordings every 15 minutes until 90 minutes after the administration of the PGE1 derivate. Results We observed seven arteries and seven veins. The diameter and blood flow of the arteries was significantly increased compared with the veins at both 60 and 75 minutes after administration of the PGE1 derivate (p Discussion The PGE1 derivate improved blood flow in the arteries but did not induce blood stasis in the veins. Our results suggest that the PGE1 derivate might be a potential therapeutic agent, as it improved blood flow in the nerve roots in a canine model of chronic cauda equina compression.

  16. Stimulation of ganglionated plexus attenuates cardiac neural remodeling and heart failure progression in a canine model of acute heart failure post-myocardial infarction.

    Science.gov (United States)

    Luo, Da; Hu, Huihui; Qin, Zhiliang; Liu, Shan; Yu, Xiaomei; Ma, Ruisong; He, Wenbo; Xie, Jing; Lu, Zhibing; He, Bo; Jiang, Hong

    2017-12-01

    Heart failure (HF) is associated with autonomic dysfunction. Vagus nerve stimulation has been shown to improve cardiac function both in HF patients and animal models of HF. The purpose of this present study is to investigate the effects of ganglionated plexus stimulation (GPS) on HF progression and autonomic remodeling in a canine model of acute HF post-myocardial infarction. Eighteen adult mongrel male dogs were randomized into the control (n=8) and GPS (n=10) groups. All dogs underwent left anterior descending artery ligation followed by 6-hour high-rate (180-220bpm) ventricular pacing to induce acute HF. Transthoracic 2-dimensional echocardiography was performed at different time points. The plasma levels of norepinephrine, B-type natriuretic peptide (BNP) and Ang-II were measured using ELISA kits. C-fos and nerve growth factor (NGF) proteins expressed in the left stellate ganglion as well as GAP43 and TH proteins expressed in the peri-infarct zone were measured using western blot. After 6h of GPS, the left ventricular end-diastolic volume, end-systolic volume and ejection fraction showed no significant differences between the 2 groups, but the interventricular septal thickness at end-systole in the GPS group was significantly higher than that in the control group. The plasma levels of norepinephrine, BNP, Ang-II were increased 1h after myocardial infarction while the increase was attenuated by GPS. The expression of c-fos and NGF proteins in the left stellate ganglion as well as GAP43 and TH proteins in cardiac peri-infarct zone in GPS group were significantly lower than that in control group. GPS inhibits cardiac sympathetic remodeling and attenuates HF progression in canines with acute HF induced by myocardial infarction and ventricular pacing. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Canine tooth size and fitness in male mandrills (Mandrillus sphinx).

    Science.gov (United States)

    Leigh, Steven R; Setchell, Joanna M; Charpentier, Marie; Knapp, Leslie A; Wickings, E Jean

    2008-07-01

    Sexual selection theory explains the evolution of exaggerated male morphologies and weaponry, but the fitness consequences of developmental and age-related changes in these features remain poorly understood. This long-term study of mandrill monkeys (Mandrillus sphinx) demonstrates how age-related changes in canine tooth weaponry and adult canine size correlate closely with male lifetime reproductive success. Combining long-term demographic and morphometric data reveals that male fitness covaries simply and directly with canine ontogeny, adult maximum size, and wear. However, fitness is largely independent of other somatometrics. Male mandrills sire offspring almost exclusively when their canines exceed approximately 30 mm, or two-thirds of average adult value (45 mm). Moreover, sires have larger canines than nonsires. The tooth diminishes through wear as animals age, corresponding with, and perhaps influencing, reproductive senescence. These factors combine to constrain male reproductive opportunities to a brief timespan, defined by the period of maximum canine length. Sexually-selected weaponry, especially when it is nonrenewable like the primate canine tooth, is intimately tied to the male life course. Our analyses of this extremely dimorphic species indicate that sexual selection is closely intertwined with growth, development, and aging, pointing to new directions for sexual selection theory. Moreover, the primate canine tooth has potential as a simple mammalian system for testing genetically-based models of aging. Finally, the tooth may record details of life histories in fossil primates, especially when sexual selection has played a role in the evolution of dimorphism.

  18. Evaluation of the biological differences of canine and human factor VIII in gene delivery: Implications in human hemophilia treatment

    Science.gov (United States)

    The canine is the most important large animal model for testing novel hemophilia A(HA) treatment. It is often necessary to use canine factor VIII (cFIII) gene or protein for the evaluation of HA treatment in the canine model. However, the different biological properties between cFVIII and human FVII...

  19. A theoretical model of the application of RF energy to the airway wall and its experimental validation

    Directory of Open Access Journals (Sweden)

    Brown Robert H

    2010-11-01

    Full Text Available Abstract Background Bronchial thermoplasty is a novel technique designed to reduce an airway's ability to contract by reducing the amount of airway smooth muscle through controlled heating of the airway wall. This method has been examined in animal models and as a treatment for asthma in human subjects. At the present time, there has been little research published about how radiofrequency (RF energy and heat is transferred to the airways of the lung during bronchial thermoplasty procedures. In this manuscript we describe a computational, theoretical model of the delivery of RF energy to the airway wall. Methods An electro-thermal finite-element-analysis model was designed to simulate the delivery of temperature controlled RF energy to airway walls of the in vivo lung. The model includes predictions of heat generation due to RF joule heating and transfer of heat within an airway wall due to thermal conduction. To implement the model, we use known physical characteristics and dimensions of the airway and lung tissues. The model predictions were tested with measurements of temperature, impedance, energy, and power in an experimental canine model. Results Model predictions of electrode temperature, voltage, and current, along with tissue impedance and delivered energy were compared to experiment measurements and were within ± 5% of experimental averages taken over 157 sample activations. The experimental results show remarkable agreement with the model predictions, and thus validate the use of this model to predict the heat generation and transfer within the airway wall following bronchial thermoplasty. Conclusions The model also demonstrated the importance of evaporation as a loss term that affected both electrical measurements and heat distribution. The model predictions showed excellent agreement with the empirical results, and thus support using the model to develop the next generation of devices for bronchial thermoplasty. Our results suggest

  20. Pulse-mediated chemotherapy enhances local control and survival in a spontaneous canine model of primary mucosal melanoma.

    Science.gov (United States)

    Spugnini, Enrico P; Dragonetti, Emanuele; Vincenzi, Bruno; Onori, Nicoletta; Citro, Gennaro; Baldi, Alfonso

    2006-02-01

    Mucosal melanomas account for 1% of all malignant melanomas in humans. Treatment options include surgery, chemotherapy, immunotherapy and radiation therapy; however, local recurrence and distant dissemination are still frequent. We treated locally aggressive spontaneous canine oral melanomas that, because of their advanced stage, were not treatable with conventional strategies. A cohort of 10 dogs with oral melanoma was enrolled over a 4-year period. The dogs received two sessions of local bleomycin, followed by the application of trains of biphasic pulses. The treatment was well tolerated and resulted in an overall response rate of 80% with 50% long-term control. Of interest, only one of the dogs died of metastatic disease, and four of the long-term survivors showed a vitiligo-like discoloration at the site of treatment, potentially suggesting a recruitment of the immune system by the therapy. Further studies are needed to characterize this approach and to determine its suitability for head and neck mucosal melanoma.

  1. Overexpression of vimentin in canine prostatic carcinoma

    DEFF Research Database (Denmark)

    Rodrigues, M M P; Rema, A; Gärtner, F

    2011-01-01

    Canine prostatic tumours exhibit similarities to those of man and may represent a useful model system to explore the mechanisms of cancer progression. Tumour progression to malignancy requires a change from an epithelial phenotype to a fibroblastic or mesenchymal phenotype. Vimentin expression...... is associated with the invasive phenotype of human prostate cancer cells. The aim of the present study was to characterize immunohistochemically the expression of vimentin by canine prostatic carcinomas. Primary carcinomas and metastatic tumour foci both showed vimentin expression. This finding suggests...... that the acquisition of the epithelial-mesenchymal transition phenotype in canine prostatic carcinoma may be characterized by the presence of mesenchymal intermediate filament (vimentin) that could lead to a higher likelihood of metastasis....

  2. A New MRI-Based Model of Heart Function with Coupled Hemodynamics and Application to Normal and Diseased Canine Left Ventricles

    Science.gov (United States)

    Choi, Young Joon; Constantino, Jason; Vedula, Vijay; Trayanova, Natalia; Mittal, Rajat

    2015-01-01

    A methodology for the simulation of heart function that combines an MRI-based model of cardiac electromechanics (CE) with a Navier–Stokes-based hemodynamics model is presented. The CE model consists of two coupled components that simulate the electrical and the mechanical functions of the heart. Accurate representations of ventricular geometry and fiber orientations are constructed from the structural magnetic resonance and the diffusion tensor MR images, respectively. The deformation of the ventricle obtained from the electromechanical model serves as input to the hemodynamics model in this one-way coupled approach via imposed kinematic wall velocity boundary conditions and at the same time, governs the blood flow into and out of the ventricular volume. The time-dependent endocardial surfaces are registered using a diffeomorphic mapping algorithm, while the intraventricular blood flow patterns are simulated using a sharp-interface immersed boundary method-based flow solver. The utility of the combined heart-function model is demonstrated by comparing the hemodynamic characteristics of a normal canine heart beating in sinus rhythm against that of the dyssynchronously beating failing heart. We also discuss the potential of coupled CE and hemodynamics models for various clinical applications. PMID:26442254

  3. Evaluation of Left Ventricular Diastolic Dysfunction with Early Systolic Dysfunction Using Two-Dimensional Speckle Tracking Echocardiography in Canine Heart Failure Model.

    Science.gov (United States)

    Wu, Wei-Chun; Ma, Hong; Xie, Rong-Ai; Gao, Li-Jian; Tang, Yue; Wang, Hao

    2016-04-01

    This study evaluated the role of two-dimensional speckle tracking echocardiography (2DSTE) for predicting left ventricular (LV) diastolic dysfunction in pacing-induced canine heart failure. Pacing systems were implanted in 8 adult mongrel dogs, and continuous rapid right ventricular pacing (RVP, 240 beats/min) was maintained for 2 weeks. The obtained measurements from 2DSTE included global strain rate during early diastole (SRe) and during late diastole (SRa) in the longitudinal (L-SRe, L-SRa), circumferential (C-SRe, C-SRa), and radial directions (R-SRe, R-SRa). Changes in heart morphology were observed by light microscopy and transmission electron microscopy at 2 weeks. The onset of LV diastolic dysfunction with early systolic dysfunction occurred 3 days after RVP initiation. Most of the strain rate imaging indices were altered at 1 or 3 days after RVP onset and continued to worsen until heart failure developed. Light and transmission electron microscopy showed myocardial vacuolar degeneration and mitochondrial swelling in the left ventricular at 2 weeks after RVP onset. Pearson's correlation analysis revealed that parameters of conventional echocardiography and 2DSTE showed moderate correlation with LV pressure parameters, including E/Esep' (r = 0.58, P echocardiography and strain rate imaging could effectively predict LV diastolic dysfunction (area under the curve: E/Esep' 0.78; L-SRe 0.84; E/L-SRe 0.80; R-SRe 0.80). 2DSTE was a sensitive and accurate technique that could be used for predicting LV diastolic dysfunction in canine heart failure model. © 2015, Wiley Periodicals, Inc.

  4. Experimental comparison of models for ultrafast impact ionization is silicon

    DEFF Research Database (Denmark)

    Tarekegne, Abebe Tilahun; Iwaszczuk, Krzysztof; Jepsen, Peter Uhd

    2016-01-01

    We compare experimentally the exponential and quadratic (Keldysh formula) impact ionization models using THz induced impact ionization in silicon. We demonstrate that the exponential model offers the best description of impact ionization process for ultrashort electric filed pulses.......We compare experimentally the exponential and quadratic (Keldysh formula) impact ionization models using THz induced impact ionization in silicon. We demonstrate that the exponential model offers the best description of impact ionization process for ultrashort electric filed pulses....

  5. Experimental modeling of swirl flows in power plants

    Science.gov (United States)

    Shtork, S. I.; Litvinov, I. V.; Gesheva, E. S.; Tsoy, M. A.; Skripkin, S. G.

    2018-03-01

    The article presents an overview of the methods and approaches to experimental modeling of various thermal and hydropower units - furnaces of pulverized coal boilers and flow-through elements of hydro turbines. The presented modeling approaches based on a combination of experimentation and rapid prototyping of working parts may be useful in optimizing energy equipment to improve safety and efficiency of industrial energy systems.

  6. Improving the physiological realism of experimental models

    NARCIS (Netherlands)

    Vinnakota, Kalyan C.; Cha, Chae Y.; Rorsman, Patrik; Balaban, Robert S.; La Gerche, Andre; Wade-Martins, Richard; Beard, Daniel A.; Jeneson, Jeroen A. L.

    The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these

  7. Experimental models of the gut microbiome

    NARCIS (Netherlands)

    Venema, K.; Abbeele, P. van den

    2013-01-01

    The human gut contains a diverse microbiota with large potential to influence health. Given the difficulty to access the main sites of the gut, in vitro models have been developed to dynamically monitor microbial processes at the site of metabolic activity. These models range from simple batch

  8. GdNCT of spontaneous canine melanoma

    International Nuclear Information System (INIS)

    Mitin, V.N.; Kulakov, V.N.; Khokhlov, V.F.

    2006-01-01

    The effectiveness of GdNCT has been studied in dogs with spontaneous melanoma of the mucousmembrane of the oral cavity patients on the NCT base at the IRT MEPhI reactor. The control group with melanomas was treated with neutrons. Fourteen canine patients were selected in the Clinic of Experimental Therapy affiliated with the RCRC RAMS. The calculation of doses has shown that the total dose of energy release depending on Gd concentration in the target can be several times higher than the dose produced by the reactor neutron beam. The calculations were carried out using the diffusion pharmacokinetic model. The gadolinium drug dipentast was administered intratumorally immediately prior to irradiation. The tumor size was estimated by measuring it in three projections. The tumor was irradiated for 60-90 minutes with a thermal neutron flux of 0.7x10 9 n/cm 2 s. The dose on tumor was 80-120 Gy, on surrounding tissues - 12-15 Gy. The treatment plan included immunotherapy with Roncoleikin in a dose of (15-10)x10 3 IE/kg. The results of GdNCT are still under observation. The results conform to those obtained by us earlier in cell cultures and inoculated experimental tumors. GdNCT is also effective in combination with immunotherapy. (author)

  9. [An experimental model of transgastric ooforectomy using a porcine model].

    Science.gov (United States)

    Tomulescu, V; Gheorghe, C; Piţigoi, D; Kosa, A; Ciocarlan, M; Pietrăreanu, D; Turcu, F; Copăescu, C; Droc, G; Popescu, H; Grigorescu, B; Stănciulea, O; Herlea, V; Popescu, I

    2010-01-01

    Transabdominal routes for surgery entail general anaesthesia with its inherent risks and complications (prolonged hospital stay, abdominal incisions that may be difficult in obese patients). Minimally invasive procedures require shorter hospitalization, have shorter recovery periods, less postoperative discomfort, and lower morbidity and complications. The purpose of this study was to use a porcine model to determine the feasibility and the safety of organ resection (oophorectomy and tubectomy). 10 Big White pigs between 25-30 kg underwent transgastric ooforectomy. The first 5 cases were performed in a hybrid procedure (laparoscopic-NOTES) in order to have a better control and supervise the maneuvers done by the mobile endoscope and to guide in the abdominal cavity. Adnexectomy was possible in all ten experiments. Full operative time (from starting endoscopy to complete gastrectomy closing) was 180 min to 270 min. The gastric defect closing was the most difficult manoever lasting from 10 min with OTSC clips to 100 using endoloops and clips. The animals have tolerated well the experiments and there have been no remarkable incidents during our 10 experments. In only one case a bleeding from gastotomy required electric coagulation. Transgastric ooforectomy in an experimental model is a procedure that requires advanced laparoscopical and endoscopical skills. Our early results are promissing. Its application in humans needs further confirmation of the method.

  10. Cooking Potatoes: Experimentation and Mathematical Modeling.

    Science.gov (United States)

    Chen, Xiao Dong

    2002-01-01

    Describes a laboratory activity involving a mathematical model of cooking potatoes that can be solved analytically. Highlights the microstructure aspects of the experiment. Provides the key aspects of the results, detailed background readings, laboratory procedures and data analyses. (MM)

  11. Optimization of experimental human leukemia models (review

    Directory of Open Access Journals (Sweden)

    D. D. Pankov

    2012-01-01

    Full Text Available Actual problem of assessing immunotherapy prospects including antigenpecific cell therapy using animal models was covered in this review.Describe the various groups of currently existing animal models and methods of their creating – from different immunodeficient mice to severalvariants of tumor cells engraftment in them. The review addresses the possibility of tumor stem cells studying using mouse models for the leukemia treatment with adoptive cell therapy including WT1. Also issues of human leukemia cells migration and proliferation in a mice withdifferent immunodeficiency degree are discussed. To assess the potential immunotherapy efficacy comparison of immunodeficient mouse model with clinical situation in oncology patients after chemotherapy is proposed.

  12. Ideal Experimental Rat Models for Liver Diseases

    OpenAIRE

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-01-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and dive...

  13. Vaccines for Canine Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Faeze Foroughi-Parvar

    2014-01-01

    Full Text Available Leishmania infantum is the obligatory intracellular parasite of mammalian macrophages and causes zoonotic visceral leishmaniasis (ZVL. The presence of infected dogs as the main reservoir host of ZVL is regarded as the most important potential risk for human infection. Thus the prevention of canine visceral leishmaniasis (CVL is essential to stop the current increase of the Mediterranean visceral leishmaniasis. Recently considerable advances in achieving protective immunization of dogs and several important attempts for achieving an effective vaccine against CVL lead to attracting the scientists trust in its important role for eradication of ZVL. This paper highlights the recent advances in vaccination against canine visceral leishmaniasis from 2007 until now.

  14. Canine Parvovirus: Current Perspective

    OpenAIRE

    Nandi, S.; Kumar, Manoj

    2010-01-01

    Canine parvovirus 2 (CPV-2) has been considered to be an important pathogen of domestic and wild canids and has spread worldwide since its emergence in 1978. It has been reported from Asia, Australia, New Zealand, the Americas and Europe. Two distinct parvoviruses are now known to infect dogs—the pathogenic CPV-2 and CPV-1 or the minute virus of canine (MVC). CPV-2, the causative agent of acute hemorrhagic enteritis and myocarditis in dogs, is one of the most important pathogenic viruses with...

  15. Ideal Experimental Rat Models for Liver Diseases.

    Science.gov (United States)

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-05-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes.

  16. Experimental Verification of the Transient Model in an Enrichment Circuit

    International Nuclear Information System (INIS)

    Fernandino, Maria; Brasnarof, Daniel; Delmastro, Dario

    2003-01-01

    In the present work an experimental closed loop representing a single stage of an uranium gaseous diffusion enrichment cascade is described, loop that is used to experimentally validate an analytical model that describes the dynamics inside such a loop.The conditions established inside the experimental loop after a few working hours were reproduced by the analytical model, leaving the slower thermal phenomena taking place for future studies.Two kinds of perturbations were experimentally introduced: a change in the range of operation of one of the compressors and the addition of mass into the loop.Numerical and experimental results are compared and presented in this work. The analytical model proposed was verified against these two changes, with very good agreement in the time response and measured values.This analytical model allows us to determine the characteristic time response of the system

  17. Scaled Experimental Modeling of VHTR Plenum Flows

    Energy Technology Data Exchange (ETDEWEB)

    ICONE 15

    2007-04-01

    Abstract The Very High Temperature Reactor (VHTR) is the leading candidate for the Next Generation Nuclear Power (NGNP) Project in the U.S. which has the goal of demonstrating the production of emissions free electricity and hydrogen by 2015. Various scaled heated gas and water flow facilities were investigated for modeling VHTR upper and lower plenum flows during the decay heat portion of a pressurized conduction-cooldown scenario and for modeling thermal mixing and stratification (“thermal striping”) in the lower plenum during normal operation. It was concluded, based on phenomena scaling and instrumentation and other practical considerations, that a heated water flow scale model facility is preferable to a heated gas flow facility and to unheated facilities which use fluids with ranges of density to simulate the density effect of heating. For a heated water flow lower plenum model, both the Richardson numbers and Reynolds numbers may be approximately matched for conduction-cooldown natural circulation conditions. Thermal mixing during normal operation may be simulated but at lower, but still fully turbulent, Reynolds numbers than in the prototype. Natural circulation flows in the upper plenum may also be simulated in a separate heated water flow facility that uses the same plumbing as the lower plenum model. However, Reynolds number scaling distortions will occur at matching Richardson numbers due primarily to the necessity of using a reduced number of channels connected to the plenum than in the prototype (which has approximately 11,000 core channels connected to the upper plenum) in an otherwise geometrically scaled model. Experiments conducted in either or both facilities will meet the objectives of providing benchmark data for the validation of codes proposed for NGNP designs and safety studies, as well as providing a better understanding of the complex flow phenomena in the plenums.

  18. Experimental modeling of a deoiling hydrocyclone system

    DEFF Research Database (Denmark)

    Bram, Mads Valentin; Hassan, Abdiladif Ahmed; Hansen, Dennis Severin

    2015-01-01

    responses of PDR via dedicated experiments a set of first-order-plus-dead-time (FOPDT) models that represent the main characteristics of the concerned hydrocyclone system is developed and analyzed for the entire operating range. The obtained multiple FOPDT models can illustrate the system performance...... acrylic hydrocyclone was tested as proof of concept for obtaining its steady-state and dynamic performances. The steady-state performance is able to provide the proportional correlation between PDR and flow split which is essential for optimizing steady-state separation efficiency. By analyzing step...

  19. Experimental and modelling studies of infiltration

    International Nuclear Information System (INIS)

    Giudici, M.

    2004-01-01

    This presentation describes a study of infiltration in the unsaturated soil with the objective of estimating the recharge to a phreatic aquifer. The study area is at the border of the city of Milan (Northern Italy), which draws water for both domestic and industrial purposes from ground water resources located beneath the urban area. The rate of water pumping from the aquifer system has been varying during the XX century, depending upon the number of inhabitants and the development of industrial activities. This caused variations with time of the depth of the water table below the ground surface and in turn some emergencies: the two most prominent episodes correspond to the middle '70s, when the water table in the city centre was about 30 m below the undisturbed natural conditions, and to the last decade, when the water table has raised at a rate of approximately 1 m/year and caused infiltrations in deep constructions (garages and building foundations, the underground railways, etc.). We have developed four ground water flow models at different scales, which share some characteristics: they are based on quasi-3D approximation (horizontal flow in the aquifers and vertical flow in the aquitards), conservative finite-differences schemes for regular grid with square cells in the horizontal plane and are implemented with proprietary computer codes. Among the problems that were studied for the development of these models, I recall some numerical problems, related to the behaviour of the phreatic aquifer under conditions of strong exploitation. Model calibration and validation for ModMil has been performed with a two-stage process, i.e., using some of the available data for model calibration and the remaining data for model validation. The application of geophysical exploration techniques, in particular seismic and geo-electrical prospecting, has been very useful to complete the data and information on the hydro-geological structure obtained from stratigraphic logs

  20. Lung cancer risk models from experimental animals

    International Nuclear Information System (INIS)

    Gilbert, E.S.

    1988-03-01

    The objective of this paper is to present analyses of data based on methods that adequately account for time-related factors and competiting risks, and that yield results that are expressed in a form comparable to results obtained from recent analyses of epidemiological studies of humans exposed to radon and radon daughters. These epidemiological analyses have modeled the hazard, or age-specific death rates, as a function of factors such as dose and dose rate, time from exposure, and time from cessation of exposure. The starting point for many of the analyses of human data has been the constant relative risk modeling which the age-specific death rates are assumed to be a function of cumulative dose, and the risks due to exposure are assumed to be proportional to the age-specific baseline death rates. However, departures from this initial model, such as dependence of risks on age at risk and/or time from exposure, have been investigated. These analyses have frequently been based on a non-parametric model that requires minimal assumptions regarding the baseline risks and their dependence on age

  1. Isothermal coarse mixing: experimental and CFD modelling

    International Nuclear Information System (INIS)

    Gilbertson, M.A.; Kenning, D.B.R.; Hall, R.W.

    1992-01-01

    A plane, two-dimensional flow apparatus has been built which uses a jet of solid 6mm diameter balls to model a jet of molten drops falling into a tank of water to study premixing prior to a vapour explosion. Preliminary experiments with unheated stainless steel balls are here compared with computational fluid dynamics (CFD) calculations by the code CHYMES. (6 figures) (Author)

  2. New experimental model of multiple myeloma.

    Science.gov (United States)

    Telegin, G B; Kalinina, A R; Ponomarenko, N A; Ovsepyan, A A; Smirnov, S V; Tsybenko, V V; Homeriki, S G

    2001-06-01

    NSO/1 (P3x63Ay 8Ut) and SP20 myeloma cells were inoculated to BALB/c OlaHsd mice. NSO/1 cells allowed adequate stage-by-stage monitoring of tumor development. The adequacy of this model was confirmed in experiments with conventional cytostatics: prospidium and cytarabine caused necrosis of tumor cells and reduced animal mortality.

  3. Ventricular, but not atrial, M2-muscarinic receptors increase in the canine pacing-overdrive model of heart failure.

    Science.gov (United States)

    Wilkinson, M; Giles, A; Armour, J A; Cardinal, R

    1996-01-01

    To investigate the effects of heart failure induced by chronic rapid ventricular pacing (six weeks) on canine atrial and ventricular muscarinic receptors. Dogs (n = 4) were fitted with a bipolar pacing electrode connected to a Medtronic pacemaker set at 240 stimuli/min. Pacing was maintained for six weeks. Tissue samples obtained from the left atrium and ventral wall of the left ventricle were frozen at -70 degrees C. Control tissue was obtained from normal dogs (n = 6) following anesthesia and thoracotomy. M2-muscarinic receptors were characterized and quantified in tissue micropunches using the hydrophilic ligand [3H] N-methyl-scopolamine (NMS). Cardiac tissue bound [3H] NMS with the specificity of an M2 subtype. Tachycardia-induced heart failure did not affect atrial muscarinic receptors but signify left ventricular myocytes (control 160.0 +/- 10.0 fmol/mg protein versus heart failure 245.0 +/- 25.0 fmol/mg protein; P failure was accompanied by an increase (+ 53%) in ventricular, but not atrial, M2 receptors compared with normal dogs.

  4. Comparison of Point Placement by Veterinary Professionals with Different Levels of Acupuncture Training in a Canine Cadaver Model.

    Science.gov (United States)

    Yang, Toni; Shmalberg, Justin; Hochman, Lindsay; Miscioscia, Erin; Brumby, Meghan; McKenna, Kelsey; Roth, Amber

    2017-10-01

    Veterinary acupuncture is becoming increasingly implemented for various disease processes, with growing numbers of veterinarians pursuing advanced training to meet the rising demand for this relatively new intervention. Accurate acupoint placement remains challenging, with individual practitioners relying on varying methods of point identification, often compounded by the transpositional nature of points for companion animals. The aim of this study was to assess for differences in acupuncture needle placement of select points between veterinary professionals with three different levels of acupuncture training in an academic teaching environment. Seven participants placed a total of six acupoints on a canine cadaver. Digital radiography was used to document each participant's point placement. Each participant's point location was then compared to a control "correct" point, and the distance between the two points was measured. A significant difference in placement accuracy was identified between the participants when grouped by training level (p = 0.03). These results indicate that veterinary patients receiving acupuncture treatment from veterinarians with different levels of training may subsequently experience varying effects, although further studies are warranted on more specific acupoint description as well as the clinical implications of needle placement accuracy. Copyright © 2017. Published by Elsevier B.V.

  5. Experimental Validation of a Permeability Model for Enrichment Membranes

    International Nuclear Information System (INIS)

    Orellano, Pablo; Brasnarof, Daniel; Florido Pablo

    2003-01-01

    An experimental loop with a real scale diffuser, in a single enrichment-stage configuration, was operated with air at different process conditions, in order to characterize the membrane permeability.Using these experimental data, an analytical geometric-and-morphologic-based model was validated.It is conclude that a new set of independent measurements, i.e. enrichment, is necessary in order to fully characterize diffusers, because of its internal parameters are not univocally determinated with permeability experimental data only

  6. New experimental model for training in videosurgery Novo modelo experimental para treinamento em videocirurgia

    Directory of Open Access Journals (Sweden)

    Danilo Malta Batista

    2012-10-01

    Full Text Available PURPOSE: To develop a new experimental model of lower cost for training in videosurgery. METHODS: This project was performed at the Nucleus of Experimental Surgery of the Bahiana School of Medicine and Public Health, based on previous models described in the literature and under the supervision of the full professor of Operative Technique and Experimental Surgery II. It was made a model cube-shaped, made of wood, with holes distributed in various locations, rubber stoppers for the holes and lined externally with carpet, and internally with laminate. RESULTS: The new experimental model is of low cost and reproduces quite faithfully several videosurgical procedures. CONCLUSION: Medical schools interested in the subject may adopt the new model for training in videosurgery without the need of high costs for making and using these models.OBJETIVO: Desenvolver um novo modelo experimental de baixo custo para treinamento em videocirurgia MÉTODOS: Este projeto foi conduzido no Núcleo de Cirurgia Experimental da Escola Bahiana de Medicina e Saúde Pública, baseado em modelos prévios descritos na literatura e sob a supervisão do professor titular de Técnica Operatória e Cirurgia Experimental II. Foi feito um modelo em formato de cubo, de madeira, com furos distribuídos em vários locais, tampas de borracha para os orifícios e forrado externamente com carpete e internamente com laminado. RESULTADOS: O novo modelo experimental desenvolvido é de baixo custo e reproduz de forma bastante fiel diversos procedimentos videocirúrgicos. CONCLUSÃO: Faculdades médicas interessadas no tema poderão adotar o novo modelo para o treinamento em videocirurgia sem que sejam necessários gastos elevados para a confecção e o uso desses modelos.

  7. Experimentally testing the standard cosmological model

    Energy Technology Data Exchange (ETDEWEB)

    Schramm, D.N. (Chicago Univ., IL (USA) Fermi National Accelerator Lab., Batavia, IL (USA))

    1990-11-01

    The standard model of cosmology, the big bang, is now being tested and confirmed to remarkable accuracy. Recent high precision measurements relate to the microwave background; and big bang nucleosynthesis. This paper focuses on the latter since that relates more directly to high energy experiments. In particular, the recent LEP (and SLC) results on the number of neutrinos are discussed as a positive laboratory test of the standard cosmology scenario. Discussion is presented on the improved light element observational data as well as the improved neutron lifetime data. alternate nucleosynthesis scenarios of decaying matter or of quark-hadron induced inhomogeneities are discussed. It is shown that when these scenarios are made to fit the observed abundances accurately, the resulting conclusions on the baryonic density relative to the critical density, {Omega}{sub b}, remain approximately the same as in the standard homogeneous case, thus, adding to the robustness of the standard model conclusion that {Omega}{sub b} {approximately} 0.06. This latter point is the deriving force behind the need for non-baryonic dark matter (assuming {Omega}{sub total} = 1) and the need for dark baryonic matter, since {Omega}{sub visible} < {Omega}{sub b}. Recent accelerator constraints on non-baryonic matter are discussed, showing that any massive cold dark matter candidate must now have a mass M{sub x} {approx gt} 20 GeV and an interaction weaker than the Z{sup 0} coupling to a neutrino. It is also noted that recent hints regarding the solar neutrino experiments coupled with the see-saw model for {nu}-masses may imply that the {nu}{sub {tau}} is a good hot dark matter candidate. 73 refs., 5 figs.

  8. Experimentally testing the standard cosmological model

    International Nuclear Information System (INIS)

    Schramm, D.N.

    1990-11-01

    The standard model of cosmology, the big bang, is now being tested and confirmed to remarkable accuracy. Recent high precision measurements relate to the microwave background; and big bang nucleosynthesis. This paper focuses on the latter since that relates more directly to high energy experiments. In particular, the recent LEP (and SLC) results on the number of neutrinos are discussed as a positive laboratory test of the standard cosmology scenario. Discussion is presented on the improved light element observational data as well as the improved neutron lifetime data. alternate nucleosynthesis scenarios of decaying matter or of quark-hadron induced inhomogeneities are discussed. It is shown that when these scenarios are made to fit the observed abundances accurately, the resulting conclusions on the baryonic density relative to the critical density, Ω b , remain approximately the same as in the standard homogeneous case, thus, adding to the robustness of the standard model conclusion that Ω b ∼ 0.06. This latter point is the deriving force behind the need for non-baryonic dark matter (assuming Ω total = 1) and the need for dark baryonic matter, since Ω visible b . Recent accelerator constraints on non-baryonic matter are discussed, showing that any massive cold dark matter candidate must now have a mass M x approx-gt 20 GeV and an interaction weaker than the Z 0 coupling to a neutrino. It is also noted that recent hints regarding the solar neutrino experiments coupled with the see-saw model for ν-masses may imply that the ν τ is a good hot dark matter candidate. 73 refs., 5 figs

  9. Experimental modeling methods in Industrial Engineering

    Directory of Open Access Journals (Sweden)

    Peter Trebuňa

    2009-03-01

    Full Text Available Dynamic approaches to a management system of the present industrial practice, forcing businesses to address management issues in-house continuous improvement of production and non-production processes. Experience has repeatedly demonstrated the need for a system approach not only in analysis but also in the planning and actual implementation of these processes. Therefore, the contribution is focused on the description of the modeling in industrial practice by a system approach, in order to avoid erroneous application of the decision to the implementation phase, and thus prevent any longer applying methods "attempt - fallacy".

  10. CS model coil experimental log book

    International Nuclear Information System (INIS)

    Nishijima, Gen; Sugimoto, Makoto; Nunoya, Yoshihiko; Wakabayashi, Hiroshi; Tsuji, Hiroshi

    2001-02-01

    Charging test of the ITER CS Model Coil which is the world's largest superconducting pulse coil and the CS Insert Coil had started at April 11, 2000 and had completed at August 18, 2000. In the campaign, total shot numbers were 356 and the size of the data file in the DAS (Data Acquisition System) was over 20 GB. This report is a database that consists of the log list and the log sheets of every shot. One can access the database, make a search, and browse results via Internet (http://1ogwww.naka.jaeri.go.jp). The database will be useful to quick search to choose necessary shots. (author)

  11. Tesla coil theoretical model and experimental verification

    OpenAIRE

    Voitkans, Janis; Voitkans, Arnis

    2014-01-01

    Abstract – In this paper a theoretical model of a Tesla coil operation is proposed. Tesla coil is described as a long line with distributed parameters in a single-wired format, where the line voltage is measured against electrically neutral space. It is shown that equivalent two-wired scheme can be found for a single-wired scheme and already known long line theory can be applied to a Tesla coil. Formulas for calculation of voltage in a Tesla coil by coordinate and calculation of resonance fre...

  12. Prostate histotripsy for BPH: initial canine results

    Science.gov (United States)

    Roberts, William W.; Hall, Timothy L.; Hempel, Christopher R.; Cain, Charles A.

    2009-02-01

    Histotripsy is an extracorporeal ablative technology that utilizes microsecond pulses of intense ultrasound (< 1% duty cycle) to produce nonthermal, mechanical fractionation of targeted tissue. We have previously demonstrated the feasibility of histotripsy prostate ablation. In this study we sought to assess the chronic tissue response, tolerability and safety of histotripsy in a chronic in vivo canine model. Five acute and thirteen chronic canine subjects were anesthetized and treated with histotripsy targeting the prostate. Pulses consisted of 3 cycle bursts of 750 kHz ultrasound at a repetition rate of 300 Hz delivered transabdominally from a highly focused 15 cm aperture array. Transrectal ultrasound imaging provided accurate targeting and real-time monitoring of histotripsy treatment. Prostates were harvested at 0, 7, 28, or 56 days after treatment. Consistent mechanical tissue fractionation and debulking of prostate tissue was seen acutely and at delayed time points without collateral injury. Urothelialization of the treatment cavity was apparent 28 days after treatment. Canine subjects tolerated histotripsy with minimal hematuria or discomfort. Only mild transient lab abnormalities were noted. Histotripsy is a promising non-invasive therapy for prostate tissue fractionation and debulking that appears safe and well tolerated without systemic side effects in the canine model.

  13. Experimental photoallergic contact dermatitis: a mouse model

    International Nuclear Information System (INIS)

    Maguire, H.C. Jr.; Kaidbey, K.

    1982-01-01

    We have induced photoallergic contact dermatitis in mice to 3,3',4',5 tetrachlorosalicylanilide (TCSA), chlorpromazine and 6-methylcoumarin. These compounds are known to produce photoallergic contact dermatitis in humans. The photoallergic contact dermatitis reaction in the mouse is immunologically specific viz. mice photosensitized to TCSA react, by photochallenge, to that compound and not to chlorpromazine, and conversely. The reaction requires UVA at both sensitization and challenge. It appears to be T-cell mediated in that it can be passively transferred to syngeneic mice by lymph node cells from actively sensitized mice, the histology of the reactions resembles that of classic allergic contact dermatitis in mice, challenge reactions are seen at 24 but not at 4 hr, and photoallergic contact dermatitis can be induced in B-cell deficient mice. The availability of a mouse model for the study of photo-ACD will facilitate the identification of pertinent control mechanisms and may aid in the management of the disease. It is likely that a bioassay for photoallergens of humans can be based on this mouse model

  14. Morphology of palatally impacted canines: A case-controlled cone-beam volumetric tomography study.

    Science.gov (United States)

    Hettiarachchi, Pilana Vithanage Kalani Shihanika; Olive, Richard John; Monsour, Paul

    2017-02-01

    The aim of this study was to investigate the relationships between an apical curvature or a hook and the crown/root ratio in subjects with and without palatally impacted maxillary canines. An experimental group of 44 patients (17 boys, 27 girls; mean age, 13.6 years) with 59 palatally impacted maxillary canines was selected from the records of patients referred to a radiology practice for cone-beam imaging. If a patient had bilateral palatally impacted canines, 1 canine was randomly selected for analysis. The palatally impacted canine group was matched for age and sex with 49 normal subjects (25 boys, 24 girls; mean age, 13.2 years) with 98 canines. Cone-beam DICOM files were imported into In Vivo imaging software (version 5.3; Anatomage, San Jose, Calif) for analysis. The angulations and linear variables of the maxillary canines were measured by using the software measurement tools. Chi-square and independent t tests were used to test for differences between the groups. The presence of a hook at the apical third and other root curvature were significantly different between the 2 groups (P <0.001 and P <0.05, respectively). Of the 44 palatally impacted canines, 16 (36.4%) had an apical hook and only 1 canine in the control group had an apical hook (1.0%). The mean root length of the palatally impacted canines was 2.66 mm shorter (P <0.001), and the mean crown/root ratio was significantly greater for the palatally impacted canines compared with the nonimpacted group (P <0.001). Palatally impacted canines have a greater tendency to develop apical hooks and are less likely to develop other root curvatures than are nonimpacted canines. Also, they have shorter roots resulting in larger crown/root ratios compared with the control group. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  15. CS model coil experimental log book

    Energy Technology Data Exchange (ETDEWEB)

    Nishijima, Gen; Sugimoto, Makoto; Nunoya, Yoshihiko; Wakabayashi, Hiroshi; Tsuji, Hiroshi [Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment

    2001-02-01

    Charging test of the ITER CS Model Coil which is the world's largest superconducting pulse coil and the CS Insert Coil had started at April 11, 2000 and had completed at August 18, 2000. In the campaign, total shot numbers were 356 and the size of the data file in the DAS (Data Acquisition System) was over 20 GB. This report is a database that consists of the log list and the log sheets of every shot. One can access the database, make a search, and browse results via Internet (http://1ogwww.naka.jaeri.go.jp). The database will be useful to quick search to choose necessary shots. (author)

  16. Microplasticity of MMC. Experimental results and modelling

    International Nuclear Information System (INIS)

    Maire, E.; Lormand, G.; Gobin, P.F.; Fougeres, R.

    1993-01-01

    The microplastic behavior of several MMC is investigated by means of tension and compression tests. This behavior is assymetric : the proportional limit is higher in tension than in compression but the work hardening rate is higher in compression. These differences are analysed in terms of maxium of the Tresca's shear stress at the interface (proportional limit) and of the emission of dislocation loops during the cooling (work hardening rate). On another hand, a model is proposed to calculate the value of the yield stress, describing the composite as a material composed of three phases : inclusion, unaffected matrix and matrix surrounding the inclusion having a gradient in the density of the thermally induced dilocations. (orig.)

  17. Experimental Tests of the Algebraic Cluster Model

    Science.gov (United States)

    Gai, Moshe

    2018-02-01

    The Algebraic Cluster Model (ACM) of Bijker and Iachello that was proposed already in 2000 has been recently applied to 12C and 16O with much success. We review the current status in 12C with the outstanding observation of the ground state rotational band composed of the spin-parity states of: 0+, 2+, 3-, 4± and 5-. The observation of the 4± parity doublet is a characteristic of (tri-atomic) molecular configuration where the three alpha- particles are arranged in an equilateral triangular configuration of a symmetric spinning top. We discuss future measurement with electron scattering, 12C(e,e’) to test the predicted B(Eλ) of the ACM.

  18. Microplasticity of MMC. Experimental results and modelling

    Energy Technology Data Exchange (ETDEWEB)

    Maire, E. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France)); Lormand, G. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France)); Gobin, P.F. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France)); Fougeres, R. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France))

    1993-11-01

    The microplastic behavior of several MMC is investigated by means of tension and compression tests. This behavior is assymetric : the proportional limit is higher in tension than in compression but the work hardening rate is higher in compression. These differences are analysed in terms of maxium of the Tresca's shear stress at the interface (proportional limit) and of the emission of dislocation loops during the cooling (work hardening rate). On another hand, a model is proposed to calculate the value of the yield stress, describing the composite as a material composed of three phases : inclusion, unaffected matrix and matrix surrounding the inclusion having a gradient in the density of the thermally induced dilocations. (orig.).

  19. Multiphysics modelling and experimental validation of high concentration photovoltaic modules

    International Nuclear Information System (INIS)

    Theristis, Marios; Fernández, Eduardo F.; Sumner, Mike; O'Donovan, Tadhg S.

    2017-01-01

    Highlights: • A multiphysics modelling approach for concentrating photovoltaics was developed. • An experimental campaign was conducted to validate the models. • The experimental results were in good agreement with the models. • The multiphysics modelling allows the concentrator’s optimisation. - Abstract: High concentration photovoltaics, equipped with high efficiency multijunction solar cells, have great potential in achieving cost-effective and clean electricity generation at utility scale. Such systems are more complex compared to conventional photovoltaics because of the multiphysics effect that is present. Modelling the power output of such systems is therefore crucial for their further market penetration. Following this line, a multiphysics modelling procedure for high concentration photovoltaics is presented in this work. It combines an open source spectral model, a single diode electrical model and a three-dimensional finite element thermal model. In order to validate the models and the multiphysics modelling procedure against actual data, an outdoor experimental campaign was conducted in Albuquerque, New Mexico using a high concentration photovoltaic monomodule that is thoroughly described in terms of its geometry and materials. The experimental results were in good agreement (within 2.7%) with the predicted maximum power point. This multiphysics approach is relatively more complex when compared to empirical models, but besides the overall performance prediction it can also provide better understanding of the physics involved in the conversion of solar irradiance into electricity. It can therefore be used for the design and optimisation of high concentration photovoltaic modules.

  20. High dose teriparatide (rPTH1-34) therapy increases callus volume and enhances radiographic healing at 8-weeks in a massive canine femoral allograft model.

    Science.gov (United States)

    Nishitani, Kohei; Mietus, Zachary; Beck, Christopher A; Ito, Hiromu; Matsuda, Shuichi; Awad, Hani A; Ehrhart, Nicole; Schwarz, Edward M

    2017-01-01

    Small animal studies have demonstrated significant high-dose recombinant parathyroid hormone1-34 (rPTH1-34) effects on intercalary allograft healing. Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH1-34 safety and efficacy in a clinically relevant canine femoral allograft model. Adult female mongrel hounds (n = 20) received a 5cm mid-diaphyseal osteotomy reconstructed with a plated allograft, and were randomized to: 1) Placebo (n = 5; daily saline), 2) Continuous rPTH1-34 (n = 7; 5 μg/kg/day s.c. from day 1-55 post-op), or 3) Delayed rPTH1-34 (n = 8; 5 μg/kg/day s.c. from day 14-28 post-op). Safety was assessed by physical behavior and blood calcium monitoring. Cone beam CT (CB-CT) was performed on days 14, 28 and 56 post-op to assess 2D cortical healing, 3D bone volume, and Union Ratio. Biomechanical testing and dynamic histomorphometry were also performed. The high drug dose was poorly tolerated, as most dogs receiving rPTH1-34 had to be given intravenous saline, and one dog died from hypercalcemia. Continuous rPTH1-34 significantly increased 2D healing and callus volumes at 4-weeks versus Placebo, and sustained the significant increase in cortical union at 8-week (p<0.05). These rPTH1-34 effects were confirmed by histomorphometry, revealing significant increases in mineral apposition rates (MAR) on host bone and graft-host junctions (p<0.05). Delayed rPTH1-34 significantly increased callus volume and MAR at 8 weeks (p<0.05). Although no biomechanical differences were observed, as expected for early healing, the results demonstrated that 2D RUST scoring significantly correlated with torsional biomechanics (p<0.01). In conclusion, 8-weeks of intermittent high-dose rPTH1-34 treatment significantly increases callus formation and accelerates bony union of intercalary massive allografts in a clinically relevant canine model, but with serious side-effects from hypercalcemia.

  1. High dose teriparatide (rPTH1-34 therapy increases callus volume and enhances radiographic healing at 8-weeks in a massive canine femoral allograft model.

    Directory of Open Access Journals (Sweden)

    Kohei Nishitani

    Full Text Available Small animal studies have demonstrated significant high-dose recombinant parathyroid hormone1-34 (rPTH1-34 effects on intercalary allograft healing. Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH1-34 safety and efficacy in a clinically relevant canine femoral allograft model. Adult female mongrel hounds (n = 20 received a 5cm mid-diaphyseal osteotomy reconstructed with a plated allograft, and were randomized to: 1 Placebo (n = 5; daily saline, 2 Continuous rPTH1-34 (n = 7; 5 μg/kg/day s.c. from day 1-55 post-op, or 3 Delayed rPTH1-34 (n = 8; 5 μg/kg/day s.c. from day 14-28 post-op. Safety was assessed by physical behavior and blood calcium monitoring. Cone beam CT (CB-CT was performed on days 14, 28 and 56 post-op to assess 2D cortical healing, 3D bone volume, and Union Ratio. Biomechanical testing and dynamic histomorphometry were also performed. The high drug dose was poorly tolerated, as most dogs receiving rPTH1-34 had to be given intravenous saline, and one dog died from hypercalcemia. Continuous rPTH1-34 significantly increased 2D healing and callus volumes at 4-weeks versus Placebo, and sustained the significant increase in cortical union at 8-week (p<0.05. These rPTH1-34 effects were confirmed by histomorphometry, revealing significant increases in mineral apposition rates (MAR on host bone and graft-host junctions (p<0.05. Delayed rPTH1-34 significantly increased callus volume and MAR at 8 weeks (p<0.05. Although no biomechanical differences were observed, as expected for early healing, the results demonstrated that 2D RUST scoring significantly correlated with torsional biomechanics (p<0.01. In conclusion, 8-weeks of intermittent high-dose rPTH1-34 treatment significantly increases callus formation and accelerates bony union of intercalary massive allografts in a clinically relevant canine model, but with serious side-effects from hypercalcemia.

  2. Experimental tests of the standard model

    International Nuclear Information System (INIS)

    Nodulman, L.

    1998-01-01

    The title implies an impossibly broad field, as the Standard Model includes the fermion matter states, as well as the forces and fields of SU(3) x SU(2) x U(1). For practical purposes, I will confine myself to electroweak unification, as discussed in the lectures of M. Herrero. Quarks and mixing were discussed in the lectures of R. Aleksan, and leptons and mixing were discussed in the lectures of K. Nakamura. I will essentially assume universality, that is flavor independence, rather than discussing tests of it. I will not pursue tests of QED beyond noting the consistency and precision of measurements of α EM in various processes including the Lamb shift, the anomalous magnetic moment (g-2) of the electron, and the quantum Hall effect. The fantastic precision and agreement of these predictions and measurements is something that convinces people that there may be something to this science enterprise. Also impressive is the success of the ''Universal Fermi Interaction'' description of beta decay processes, or in more modern parlance, weak charged current interactions. With one coupling constant G F , most precisely determined in muon decay, a huge number of nuclear instabilities are described. The slightly slow rate for neutron beta decay was one of the initial pieces of evidence for Cabbibo mixing, now generalized so that all charged current decays of any flavor are covered

  3. The avian-origin H3N2 canine influenza virus has limited replication in swine

    Science.gov (United States)

    A genetically and antigenically distinct H3N2 canine influenza of avian-origin was detected in March of 2015 in Chicago, Illinois. A subsequent outbreak was reported with over 1,000 dogs in the Midwest affected. The potential for canine-to-swine transmission was unknown. Experimental infection in pi...

  4. Effect of laser wavelength and protein solder concentration on acute tissue repair using laser welding: initial results in a canine ureter model.

    Science.gov (United States)

    Wright, E J; Poppas, D P

    1997-01-01

    Successful tissue approximation can be performed using low power laser energy combined with human albumin solder. In vitro studies were undertaken to investigate the acute repair strengths achieved using different laser wavelengths. Furthermore, we evaluated the change in repair strength with that resulted from changes in protein solder concentration. Intraluminal bursting pressure following ureterotomy repair was measured for the following laser wavelengths: 532, 808, 1,320, 2,100, and 10,600 nm. The tissue absorption characteristics of the 808-nm diode and the KTP-532-nm lasers required the addition of the exogenous chromophores indocyanine green and fluorescein, respectively. A 40% human albumin solder was incorporated in the repair of a 1.0-cm longitudinal defect in the canine ureter. Following determination of an optimal welding wavelength, human albumin solder of varying concentrations (25%, 38%, 45%, and 50%) were prepared and tested. The 1,320-nm YAG laser achieved the highest acute bursting pressure and was the most effective in this model. Of the concentrations of albumin tested, 50% human albumin yielded the greatest bursting pressures. We conclude that of the laser wavelengths evaluated, the 1,320-nm YAG achieves the strongest tissue weld in the acute ex vivo dog ureter model. In addition, when this laser system is used, the acute strength of a photothermal weld appears to be directly proportional to the concentration of human albumin solder in the range of 25 to 50%.

  5. Canine distemper virus (CDV) infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection.

    Science.gov (United States)

    Stephensen, C B; Welter, J; Thaker, S R; Taylor, J; Tartaglia, J; Paoletti, E

    1997-02-01

    Canine distemper virus (CDV) infection of ferrets causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system (CNS). We have tested candidate CDV vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the highly attenuated NYVAC strain of vaccinia virus and in the ALVAC strain of canarypox virus, which does not productively replicate in mammalian hosts. Juvenile ferrets were vaccinated twice with these constructs, or with an attenuated live-virus vaccine, while controls received saline or the NYVAC and ALVAC vectors expressing rabies virus glycoprotein. Control animals did not develop neutralizing antibody and succumbed to distemper after developing fever, weight loss, leukocytopenia, decreased activity, conjunctivitis, an erythematous rash typical of distemper, CNS signs, and viremia in peripheral blood mononuclear cells (as measured by reverse transcription-PCR). All three CDV vaccines elicited neutralizing titers of at least 1:96. All vaccinated ferrets survived, and none developed viremia. Both recombinant vaccines also protected against the development of symptomatic distemper. However, ferrets receiving the live-virus vaccine lost weight, became lymphocytopenic, and developed the erythematous rash typical of CDV. These data show that ferrets are an excellent model for evaluating the ability of CDV vaccines to protect against symptomatic infection. Because the pathogenesis and clinical course of CDV infection of ferrets is quite similar to that of other Morbillivirus infections, including measles, this model will be useful in testing new candidate Morbillivirus vaccines.

  6. Renal denervation using catheter-based radiofrequency ablation with temperature control: renovascular safety profile and underlying mechanisms in a hypertensive canine model.

    Science.gov (United States)

    Li, Huijie; Yu, Hang; Zeng, Chunyu; Fang, Yuqiang; He, Duofen; Zhang, Xiaoqun; Wen, Chunlan; Yang, Chengming

    2015-01-01

    Renal denervation is a novel method for hypertension treatment. In this study, we aimed to investigate the safety and efficacy of radiofrequency ablation (RFA) at ablation temperatures of 45 °C or 50 °C and its possible mechanisms. A hypertensive canine model was established by abdominal aortic constriction in 20 healthy hybrid dogs. These dogs were then randomly assigned to the treatment and the control groups, with dogs in the treatment group further randomly assigned to receive RFA at ablation temperatures of 45 °C or 50 °C. In the treatment group, RFA was performed at 1 month after modeling; renal angiography was performed at 2 months after ablation. The arterial vessels of the dogs were examined histologically with hematoxylin and eosin staining. Changes in blood pressure in the foreleg and whole-body norepinephrine spillover rate were also assessed. No arterial stenosis, dissection, thrombosis or other abnormalities were detected in the treated vessels by renal angiography, yet histology results showed minimal to mild renal arterial injury. Renal denervation resulted in a marked decrease in the whole-body norepinephrine spillover rate (p 0.05). Renal denervation can be performed without acute major adverse events, using catheter-based RFA with temperature control. The procedure was feasible in reducing blood pressure by at least partially inhibiting sympathetic drive and systemic sympathetic outflow.

  7. Mutant mice: experimental organisms as materialised models in biomedicine.

    Science.gov (United States)

    Huber, Lara; Keuck, Lara K

    2013-09-01

    Animal models have received particular attention as key examples of material models. In this paper, we argue that the specificities of establishing animal models-acknowledging their status as living beings and as epistemological tools-necessitate a more complex account of animal models as materialised models. This becomes particularly evident in animal-based models of diseases that only occur in humans: in these cases, the representational relation between animal model and human patient needs to be generated and validated. The first part of this paper presents an account of how disease-specific animal models are established by drawing on the example of transgenic mice models for Alzheimer's disease. We will introduce an account of validation that involves a three-fold process including (1) from human being to experimental organism; (2) from experimental organism to animal model; and (3) from animal model to human patient. This process draws upon clinical relevance as much as scientific practices and results in disease-specific, yet incomplete, animal models. The second part of this paper argues that the incompleteness of models can be described in terms of multi-level abstractions. We qualify this notion by pointing to different experimental techniques and targets of modelling, which give rise to a plurality of models for a specific disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Activation patterns of Purkinje fibers during long-duration ventricular fibrillation in an isolated canine heart model.

    Science.gov (United States)

    Tabereaux, Paul B; Walcott, Greg P; Rogers, Jack M; Kim, Jong; Dosdall, Derek J; Robertson, Peter G; Killingsworth, Cheryl R; Smith, William M; Ideker, Raymond E

    2007-09-04

    The roles of Purkinje fibers (PFs) and focal wave fronts, if any, in the maintenance of ventricular fibrillation (VF) are unknown. If PFs are involved in VF maintenance, it should be possible to map wave fronts propagating from PFs into the working ventricular myocardium during VF. If wave fronts ever arise focally during VF, it should be possible to map them appearing de novo. Six canine hearts were isolated, and the left main coronary artery was cannulated and perfused. The left ventricular cavity was exposed, which allowed direct endocardial mapping of the anterior papillary muscle insertion. Nonperfused VF was induced, and 6 segments of data, each 5 seconds long, were analyzed during 10 minutes of VF. During 36 segments of data that were analyzed, 1018 PF or focal wave fronts of activation were identified. In 534 wave fronts, activation was mapped propagating from working ventricular myocardium to PF. In 142 wave fronts, activation was mapped propagating from PF to working ventricular myocardium. In 342 wave fronts, activation was mapped arising focally. More than 1 of these 3 patterns could occur in the same wave front. PFs are highly active throughout the first 10 minutes of VF. In addition to retrograde propagation from the working ventricular myocardium to PFs, antegrade propagation occurs from PFs to working ventricular myocardium, which suggests PFs are important in VF maintenance. Prior plunge needle recordings in dogs indicate activation propagates from the endocardium toward the epicardium after 1 minute of VF, which suggests that focal sites on the endocardium may represent foci and not breakthrough. If so, in addition to reentry, abnormal automaticity or triggered activity may also occur during VF.

  9. Testing Experimental Compounds against Leishmaniansis in Laboratory Animal Model Systems

    Science.gov (United States)

    1984-09-01

    consulted in five human and two canine cases of suspected leishmaniasis. Two of the 5 human cases were isoenzyme typed as L. b. braziliensis ( Peru ...animal. The latter may be of use in controlling some of the complications of diabetes . %’Wr WF ’ 56 PU BLICAT I ONS_ Griffith, O.W., "Mechanism of

  10. Morphofunctional analysis of experimental model of esophageal achalasia in rats.

    Science.gov (United States)

    Sabirov, A G; Raginov, I S; Burmistrov, M V; Chelyshev, Y A; Khasanov, R Sh; Moroshek, A A; Grigoriev, P N; Zefirov, A L; Mukhamedyarov, M A

    2010-10-01

    We carried out a detailed analysis of rat model of esophageal achalasia previously developed by us. Manifest morphological and functional disorders were observed in experimental achalasia: hyperplasia of the squamous epithelium, reduced number of nerve fibers, excessive growth of fibrous connective tissue in the esophageal wall, high contractile activity of the lower esophageal sphincter, and reduced motility of the longitudinal muscle layer. Changes in rat esophagus observed in experimental achalasia largely correlate with those in esophageal achalasia in humans. Hence, our experimental model can be used for the development of new methods of disease treatment.

  11. The experimental and shell model approach to 100Sn

    International Nuclear Information System (INIS)

    Grawe, H.; Maier, K.H.; Fitzgerald, J.B.; Heese, J.; Spohr, K.; Schubart, R.; Gorska, M.; Rejmund, M.

    1995-01-01

    The present status of experimental approach to 100 Sn and its shell model structure is given. New developments in experimental techniques, such as low background isomer spectroscopy and charged particle detection in 4π are surveyed. Based on recent experimental data shell model calculations are used to predict the structure of the single- and two-nucleon neighbours of 100 Sn. The results are compared to the systematic of Coulomb energies and spin-orbit splitting and discussed with respect to future experiments. (author). 51 refs, 11 figs, 1 tab

  12. TU-CD-BRA-08: Single-Energy Computed Tomography-Based Pulmonary Perfusion Imaging: Proof-Of-Principle in a Canine Model

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, T; Boone, J [University of California Davis School of Medicine, Sacramento, CA (United States); Kent, M; Wisner, E [University of California Davis School of Veterinary Medicine, Davis, CA (United States); Fujita, Y [Tokai University, Isehara (Japan)

    2015-06-15

    Purpose: Pulmonary perfusion imaging has provided significant insights into pulmonary diseases, and can be useful in radiotherapy. The purpose of this study was to prospectively establish proof-of-principle in a canine model for single-energy CT-based perfusion imaging, which has the potential for widespread clinical implementation. Methods: Single-energy CT perfusion imaging is based on: (1) acquisition of inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast medium, (2) deformable image registration (DIR) of the two CT image data sets, and (3) subtraction of the pre-contrast image from post-contrast image, yielding a map of Hounsfield unit (HU) enhancement. These subtraction image data sets hypothetically represent perfused blood volume, a surrogate for perfusion. In an IACUC-approved clinical trial, we acquired pre- and post-contrast CT scans in the prone posture for six anesthetized, mechanically-ventilated dogs. The elastix algorithm was used for DIR. The registration accuracy was quantified using the target registration errors (TREs) for 50 pulmonary landmarks in each dog. The gradient of HU enhancement between gravity-dependent (ventral) and non-dependent (dorsal) regions was evaluated to quantify the known effect of gravity, i.e., greater perfusion in ventral regions. Results: The lung volume difference between the two scans was 4.3±3.5% on average (range 0.3%–10.1%). DIR demonstrated an average TRE of 0.7±1.0 mm. HU enhancement in lung parenchyma was 34±10 HU on average and varied considerably between individual dogs, indicating the need for improvement of the contrast injection protocol. HU enhancement in ventral (gravity-dependent) regions was found to be greater than in dorsal regions. A population average ventral-to-dorsal gradient of HU enhancement was strong (R{sup 2}=0.94) and statistically significant (p<0.01). Conclusion: This canine study demonstrated relatively accurate DIR and a strong ventral

  13. TU-CD-BRA-08: Single-Energy Computed Tomography-Based Pulmonary Perfusion Imaging: Proof-Of-Principle in a Canine Model

    International Nuclear Information System (INIS)

    Yamamoto, T; Boone, J; Kent, M; Wisner, E; Fujita, Y

    2015-01-01

    Purpose: Pulmonary perfusion imaging has provided significant insights into pulmonary diseases, and can be useful in radiotherapy. The purpose of this study was to prospectively establish proof-of-principle in a canine model for single-energy CT-based perfusion imaging, which has the potential for widespread clinical implementation. Methods: Single-energy CT perfusion imaging is based on: (1) acquisition of inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast medium, (2) deformable image registration (DIR) of the two CT image data sets, and (3) subtraction of the pre-contrast image from post-contrast image, yielding a map of Hounsfield unit (HU) enhancement. These subtraction image data sets hypothetically represent perfused blood volume, a surrogate for perfusion. In an IACUC-approved clinical trial, we acquired pre- and post-contrast CT scans in the prone posture for six anesthetized, mechanically-ventilated dogs. The elastix algorithm was used for DIR. The registration accuracy was quantified using the target registration errors (TREs) for 50 pulmonary landmarks in each dog. The gradient of HU enhancement between gravity-dependent (ventral) and non-dependent (dorsal) regions was evaluated to quantify the known effect of gravity, i.e., greater perfusion in ventral regions. Results: The lung volume difference between the two scans was 4.3±3.5% on average (range 0.3%–10.1%). DIR demonstrated an average TRE of 0.7±1.0 mm. HU enhancement in lung parenchyma was 34±10 HU on average and varied considerably between individual dogs, indicating the need for improvement of the contrast injection protocol. HU enhancement in ventral (gravity-dependent) regions was found to be greater than in dorsal regions. A population average ventral-to-dorsal gradient of HU enhancement was strong (R"2=0.94) and statistically significant (p<0.01). Conclusion: This canine study demonstrated relatively accurate DIR and a strong ventral

  14. Endogenous opioid antagonism in physiological experimental pain models

    DEFF Research Database (Denmark)

    Werner, Mads U; Pereira, Manuel P; Andersen, Lars Peter H

    2015-01-01

    hyperalgesia models (6 studies), 'pain' models (25 studies), summation models (2 studies), nociceptive reflex models (3 studies) and miscellaneous models (2 studies). A consistent reversal of analgesia by a MOR-antagonist was demonstrated in 10 of the 25 ITP-studies, including stress-induced analgesia and r...... ratings, threshold assessments and somatosensory evoked potentials (SSEP), did not appear consistent in 28 out of 32 'pain' model studies. In conclusion, only in 2 experimental human pain models, i.e., stress-induced analgesia and rTMS, administration of MOR-antagonist demonstrated a consistent effect......Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR) antagonists in placebo-controlled, double...

  15. Current practices and research updates on diabetes mellitus in canine

    Directory of Open Access Journals (Sweden)

    Pankaj Kumar

    2014-11-01

    Full Text Available Diabetes has evidence in ancient literatures, though recently is being considered as one amongst the most emerging disease condition in both human and companion animals. Diabetes mellitus is one of the common endocrinopathy of dog characterized by hyperglycemia, glycosuria and weight loss. Reports suggests high fraction of canine population suffer with diabetes world over. Studies in different veterinary hospitals of United States suggest increase in cases of canine diabetes and decrease in case fatality rate over time. Increase in cases of canine diabetes worldwide is attributed to awareness amongst pet owners, better veterinary health facilities, breed preferences by dog owners, increase dependence on commercial feeds, obesity, etc. Diabetes in most dogs is immune mediated and insulin dependent. Breed predisposition in canine is attributed to dog leukocyte antigen gene pool encoding form major histocompatibility complex-II molecules, however research is still underway. Diagnosis of diabetes still relies on blood sugar evaluation for screening of canine population, though many other diagnostic methods have shown promising benefits including measurement of fructosamine and glycated haemoglobin. Management of diabetes in dog is based on insulin therapy, diet modification and exercise. Use of oral anti-diabetics drugs in canine is limited though experimental studies have shown promising results. Alternative therapies have been explored, but only a few approaches have shown promise for clinical application.

  16. [1-11C]octanoate as a PET tracer for studying ischemic stroke. Evaluation in a canine model of thromboembolic stroke with positron emission tomography

    International Nuclear Information System (INIS)

    Kuge, Yuji; Kawashima, Hidefumi; Minematsu, Kazuo

    2000-01-01

    Octanoate is taken up by the brain and converted in astrocytes to glutamine through the TCA cycle after β-oxidation. Consequently, [1- 11 C]octanoate might serve as a useful positron emission tomography (PET) probe for studying cerebral oxidative metabolism and/or astroglial functions. The present study attempted to evaluate the utility of using [1- 11 C]octanoate as a PET tracer for imaging and evaluating the pathophysiology of ischemic stroke. We used a canine model of thromboembolic stroke. Five male beagle dogs were implanted with an indwelling catheter in the left internal carotid artery. A single autologous blood clot was injected into the left internal carotid artery through the catheter. The brain distribution of [1- 11 C]octanoate and cerebral blood flow (CBF) were determined 24 h after insult using a high resolution PET scanner. Post mortem brain regions unstained with 2, 3, 5-triphenyltetrazolium chloride (TTC) were defined as infarcts. In the region of an infarct, accumulation of [1- 11 C]octanoate decreased concurrently with CBF reduction. In contrast, normal accumulation of [1- 11 C]octanoate was observed in ischemic but vital regions, suggesting that an increased accumulation of [1- 11 C]octanoate relative to CBF takes place in these regions. In conclusion, [1- 11 C]octanoate accumulated in ischemic but vital regions, indicating that [1- 11 C]octanoate is a potentially useful PET tracer for imaging and evaluating the pathophysiology of ischemic stroke. (author)

  17. Arginase-1 expressing microglia in close proximity to motor neurons were increased early in disease progression in canine degenerative myelopathy, a model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Toedebusch, Christine M; Snyder, John C; Jones, Maria R; Garcia, Virginia B; Johnson, Gayle C; Villalón, Eric L; Coates, Joan R; Garcia, Michael L

    2018-04-01

    Toxicity within superoxide dismutase-1 (SOD1)-associated familial amyotrophic lateral sclerosis (ALS) is non-cell autonomous with direct contribution from microglia. Microglia exhibit variable expression of neuroprotective and neurotoxic molecules throughout disease progression. The mechanisms regulating microglial phenotype within ALS are not well understood. This work presents a first study to examine the specific microglial phenotypic response in close association to motor neurons in a naturally occurring disease model of ALS, canine degenerative myelopathy (DM). Microglia closely associated with motor neurons were increased in all stages of DM progression, although only DM Late reached statistical significance. Furthermore, the number of arginase-1 expressing microglia per motor neuron were significantly increased in early stages of DM, whereas the number of inducible nitric oxide synthase (iNOS)-expressing microglia per motor neuron was indistinguishable from aged controls at all stages of disease. Fractalkine, a chemotactic molecule for microglia, was expressed in motor neurons, and the fractalkine receptor was specifically localized to microglia. However, we found no correlation between microglial response and lumbar spinal cord fractalkine levels. Taken together, these data suggest that arginase-1-expressing microglia are recruited to the motor neuron early in DM disease through a fractalkine-independent mechanism. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Sustained Thromboresistant Bioactivity with Reduced Intimal Hyperplasia of Heparin-Bonded Polytetrafluoroethylene Propaten Graft in a Chronic Canine Femoral Artery Bypass Model.

    Science.gov (United States)

    Freeman, John; Chen, Aaron; Weinberg, Roy J; Okada, Tamuru; Chen, Changyi; Lin, Peter H

    2018-05-01

    Bypass graft thrombosis remains a significant mode of failure in prosthetic graft revascularization. The purpose of this investigation was to evaluate the long-term thromboresistant effect of heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft using Carmeda BioActive Surface technology in a canine model. Bilateral femorofemoral artery bypass grafts with ePTFE grafts were performed in 25 adult grayhound dogs. In each animal, a heparin-bonded ePTFE graft (Propaten, WL Gore) was placed on one side, whereas a control nonheparin graft was placed on the contralateral side. The graft patency was assessed at 1, 6, 12, 18, and 24 months (n = 5 per group) following the bypass. Heparin bioactivity of the graft material was analyzed. The effect of intimal hyperplasia was also assessed. All bypass grafts were patent at 1 month. Significantly greater patency rates were noted in the Propaten group compared to the control group at 12, 18, and 24 months, which were 84%, 80%, and 80% vs. 55%, 35%, and 20%, respectively (P  0.05). Heparin-bonded ePTFE graft provides a thromboresistant surface and reduced anastomotic intimal hyperplasia at 2 years. The stable heparin bioactivity of the Propaten graft confers an advantage in long-term graft patency. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Long-term Efficacy and Biocompatibility of Encapsulated Islet Transplantation With Chitosan-Coated Alginate Capsules in Mice and Canine Models of Diabetes.

    Science.gov (United States)

    Yang, Hae Kyung; Ham, Dong-Sik; Park, Heon-Seok; Rhee, Marie; You, Young Hye; Kim, Min Jung; Shin, Juyoung; Kim, On-You; Khang, Gilson; Hong, Tae Ho; Kim, Ji-Won; Lee, Seung-Hwan; Cho, Jae-Hyoung; Yoon, Kun-Ho

    2016-02-01

    Clinical application of encapsulated islet transplantation is hindered by low biocompatibility of capsules leading to pericapsular fibrosis and decreased islet viability. To improve biocompatibility, we designed a novel chitosan-coated alginate capsules and compared them to uncoated alginate capsules. Alginate capsules were formed by crosslinking with BaCl2, then they were suspended in chitosan solution for 10 minutes at pH 4.5. Xenogeneic islet transplantation, using encapsulated porcine islets in 1,3-galactosyltransferase knockout mice, and allogeneic islet transplantation, using encapsulated canine islets in beagles, were performed without immunosuppressants. The chitosan-alginate capsules showed similar pore size, islet viability, and insulin secretory function compared to alginate capsules, in vitro. Xenogeneic transplantation of chitosan-alginate capsules demonstrated a trend toward superior graft survival (P = 0.07) with significantly less pericapsular fibrosis (cell adhesion score: 3.77 ± 0.41 vs 8.08 ± 0.05; P transplantation. Allogeneic transplantation of chitosan-alginate capsules normalized the blood glucose level up to 1 year with little evidence of pericapsular fibrotic overgrowth on graft explantation. The efficacy and biocompatibility of chitosan-alginate capsules were demonstrated in xenogeneic and allogeneic islet transplantations using small and large animal models of diabetes. This capsule might be a potential candidate applicable in the treatment of type 1 diabetes mellitus patients, and further studies in nonhuman primates are required.

  20. Chronic administration of a leupeptin-derived calpain inhibitor fails to ameliorate severe muscle pathology in a canine model of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Martin K Childers

    2012-01-01

    Full Text Available Calpains likely play a role in the pathogenesis of Duchenne muscular dystrophy (DMD. Accordingly, calpain inhibition may provide therapeutic benefit to DMD patients. In the present study, we sought to measure benefit from administration of a novel calpain inhibitor, C101, in a canine muscular dystrophy model. Specifically, we tested the hypothesis that treatment with C101 mitigates progressive weakness and severe muscle pathology observed in young dogs with golden retriever muscular dystrophy (GRMD. Young (6 week-old GRMD dogs were treated daily with either C101 (17mg/kg twice daily oral dose, n=9 or placebo (vehicle only, n=7 for 8 weeks. A battery of functional tests, including tibiotarsal joint angle, muscle/fat composition, and pelvic limb muscle strength were performed at baseline and every two weeks during the 8-week study. Results indicate that C101-treated GRMD dogs maintained strength in their cranial pelvic limb muscles (tibiotarsal flexors while placebo-treated dogs progressively lost strength. However, concomitant improvement was not observed in posterior pelvic limb muscles (tibiotarsal extensors. C101 treatment did not mitigate force drop following repeated eccentric contractions and no improvement was seen in the development of joint contractures, lean muscle mass or muscle histopathology. Taken together, these data do not support the hypothesis that treatment with C101 mitigates progressive weakness or ameliorates severe muscle pathology observed in young dogs with GRMD.

  1. Review for 'Nattoh' model and experimental findings during cold fusion

    International Nuclear Information System (INIS)

    Matsumoto, Takaaki

    1993-01-01

    A review is described for the Nattoh model that provides the framework of the mechanisms of cold fusion. The model classifies the reactions into two categories: fundamental and associated reactions. The former involves the new 'hydrogen-catalyzed' fusion reaction and the chain-reactions of hydrogens. And extremely exciting physics are involved in the latter. Furthermore experimental findings are described. (author)

  2. Absolute quantitation of myocardial blood flow with {sup 201}Tl and dynamic SPECT in canine: optimisation and validation of kinetic modelling

    Energy Technology Data Exchange (ETDEWEB)

    Iida, Hidehiro; Kim, Kyeong-Min; Nakazawa, Mayumi; Sohlberg, Antti; Zeniya, Tsutomu; Hayashi, Takuya; Watabe, Hiroshi [National Cardiovascular Center Research Institute, Department of Investigative Radiology, Suita City, Osaka (Japan); Eberl, Stefan [National Cardiovascular Center Research Institute, Department of Investigative Radiology, Suita City, Osaka (Japan); Royal Prince Alfred Hospital, PET and Nuclear Medicine Department, Camperdown, NSW (Australia); Tamura, Yoshikazu [Akita Kumiai General Hospital, Department of Cardiology, Akita City (Japan); Ono, Yukihiko [Akita Research Institute of Brain, Akita City (Japan)

    2008-05-15

    {sup 201}Tl has been extensively used for myocardial perfusion and viability assessment. Unlike {sup 99m}Tc-labelled agents, such as {sup 99m}Tc-sestamibi and {sup 99m}Tc-tetrofosmine, the regional concentration of {sup 201}Tl varies with time. This study is intended to validate a kinetic modelling approach for in vivo quantitative estimation of regional myocardial blood flow (MBF) and volume of distribution of {sup 201}Tl using dynamic SPECT. Dynamic SPECT was carried out on 20 normal canines after the intravenous administration of {sup 201}Tl using a commercial SPECT system. Seven animals were studied at rest, nine during adenosine infusion, and four after beta-blocker administration. Quantitative images were reconstructed with a previously validated technique, employing OS-EM with attenuation-correction, and transmission-dependent convolution subtraction scatter correction. Measured regional time-activity curves in myocardial segments were fitted to two- and three-compartment models. Regional MBF was defined as the influx rate constant (K{sub 1}) with corrections for the partial volume effect, haematocrit and limited first-pass extraction fraction, and was compared with that determined from radio-labelled microspheres experiments. Regional time-activity curves responded well to pharmacological stress. Quantitative MBF values were higher with adenosine and decreased after beta-blocker compared to a resting condition. MBFs obtained with SPECT (MBF{sub SPECT}) correlated well with the MBF values obtained by the radio-labelled microspheres (MBF{sub MS}) (MBF{sub SPECT} = -0.067 + 1.042 x MBF{sub MS}, p < 0.001). The three-compartment model provided better fit than the two-compartment model, but the difference in MBF values between the two methods was small and could be accounted for with a simple linear regression. Absolute quantitation of regional MBF, for a wide physiological flow range, appears to be feasible using {sup 201}Tl and dynamic SPECT. (orig.)

  3. Experimental study and modeling of a novel magnetorheological elastomer isolator

    International Nuclear Information System (INIS)

    Yang, Jian; Li, Weihua; Sun, Shuaishuai; Du, Haiping; Li, Yancheng; Li, Jianchun; Deng, H X

    2013-01-01

    This paper reports an experimental setup aiming at evaluating the performance of a newly designed magnetorheological elastomer (MRE) seismic isolator. As a further effort to explore the field-dependent stiffness/damping properties of the MRE isolator, a series of experimental testing were conducted. Based upon the analysis of the experimental responses and the characteristics of the MRE isolator, a new model that is capable of reproducing the unique MRE isolator dynamics behaviors is proposed. The validation results verify the model’s effectiveness to portray the MRE isolator. A study on the field-dependent parameters is then provided to make the model valid with fluctuating magnetic fields. To fully explore the mechanism of the proposed model, an investigation relating the dependence of the proposed model on every parameter is carried out. (technical note)

  4. Experimental models of hepatotoxicity related to acute liver failure

    Energy Technology Data Exchange (ETDEWEB)

    Maes, Michaël [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Vinken, Mathieu, E-mail: mvinken@vub.ac.be [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Jaeschke, Hartmut [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City (United States)

    2016-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. - Highlights: • The murine APAP model is very close to what is observed in patients. • The Gal/ET model is useful to study TNFα-mediated apoptotic signaling mechanisms. • Fas receptor activation is an effective model of apoptosis and secondary necrosis. • The ConA model is a relevant model of auto-immune hepatitis and viral hepatitis. • Multiple time point evaluation needed in experimental models of acute liver injury.

  5. The Comparative Diagnostic Features of Canine and Human Lymphoma

    Directory of Open Access Journals (Sweden)

    Davis M. Seelig

    2016-06-01

    Full Text Available The non-Hodgkin lymphomas (NHLs are a heterogeneous family of lymphoid malignancies that are among the most common neoplasms of both dogs and humans. Owing to shared molecular, signaling, incidence, and pathologic features, there is a strong framework supporting the utilization of canine lymphoma as a comparative, large animal model of human NHL. In alignment with the biologic similarities, the current approach towards the diagnosis and classification of canine lymphoma is based upon the human World Health Organization guidelines. While this approach has contributed to an increasing appreciation of the potential biological scope of canine lymphoma, it has also become apparent that the most appropriate diagnostic philosophy must be multimodal, namely by requiring knowledge of microscopic, immunophenotypic, and clinical features before establishing a final disease diagnosis. This review seeks to illustrate the comparative similarities and differences in the diagnosis of canine lymphoma through the presentation of the microscopic and immunophenotypic features of its most common forms.

  6. The Comparative Diagnostic Features of Canine and Human Lymphoma.

    Science.gov (United States)

    Seelig, Davis M; Avery, Anne C; Ehrhart, E J; Linden, Michael A

    2016-06-01

    The non-Hodgkin lymphomas (NHLs) are a heterogeneous family of lymphoid malignancies that are among the most common neoplasms of both dogs and humans. Owing to shared molecular, signaling, incidence, and pathologic features, there is a strong framework supporting the utilization of canine lymphoma as a comparative, large animal model of human NHL. In alignment with the biologic similarities, the current approach towards the diagnosis and classification of canine lymphoma is based upon the human World Health Organization guidelines. While this approach has contributed to an increasing appreciation of the potential biological scope of canine lymphoma, it has also become apparent that the most appropriate diagnostic philosophy must be multimodal, namely by requiring knowledge of microscopic, immunophenotypic, and clinical features before establishing a final disease diagnosis. This review seeks to illustrate the comparative similarities and differences in the diagnosis of canine lymphoma through the presentation of the microscopic and immunophenotypic features of its most common forms.

  7. Canine parvovirus: current perspective.

    Science.gov (United States)

    Nandi, S; Kumar, Manoj

    2010-06-01

    Canine parvovirus 2 (CPV-2) has been considered to be an important pathogen of domestic and wild canids and has spread worldwide since its emergence in 1978. It has been reported from Asia, Australia, New Zealand, the Americas and Europe. Two distinct parvoviruses are now known to infect dogs-the pathogenic CPV-2 and CPV-1 or the minute virus of canine (MVC). CPV-2, the causative agent of acute hemorrhagic enteritis and myocarditis in dogs, is one of the most important pathogenic viruses with high morbidity (100%) and frequent mortality up to 10% in adult dogs and 91% in pups. The disease condition has been complicated further due to emergence of a number of variants namely CPV-2a, CPV-2b and CPV-2c over the years and involvement of domestic and wild canines. There are a number of different serological and molecular tests available for prompt, specific and accurate diagnosis of the disease. Further, both live attenuated and inactivated vaccines are available to control the disease in animals. Besides, new generation vaccines namely recombinant vaccine, peptide vaccine and DNA vaccine are in different stages of development and offer hope for better management of the disease in canines. However, new generation vaccines have not been issued license to be used in the field condition. Again, the presence of maternal antibodies often interferes with the active immunization with live attenuated vaccine and there always exists a window of susceptibility in spite of following proper immunization regimen. Lastly, judicious use of the vaccines in pet dogs, stray dogs and wild canids keeping in mind the new variants of the CPV-2 along with the proper sanitation and disinfection practices must be implemented for the successful control the disease.

  8. Using an experimental model for the study of therapeutic touch.

    Science.gov (United States)

    dos Santos, Daniella Soares; Marta, Ilda Estéfani Ribeiro; Cárnio, Evelin Capellari; de Quadros, Andreza Urba; Cunha, Thiago Mattar; de Carvalho, Emilia Campos

    2013-02-01

    to verify whether the Paw Edema Model can be used in investigations about the effects of Therapeutic Touch on inflammation by measuring the variables pain, edema and neutrophil migration. this is a pilot and experimental study, involving ten male mice of the same genetic strain and divided into experimental and control group, submitted to the chemical induction of local inflammation in the right back paw. The experimental group received a daily administration of Therapeutic Touch for 15 minutes during three days. the data showed statistically significant differences in the nociceptive threshold and in the paw circumference of the animals from the experimental group on the second day of the experiment. the experiment model involving animals can contribute to study the effects of Therapeutic Touch on inflammation, and adjustments are suggested in the treatment duration, number of sessions and experiment duration.

  9. Development of a fault test experimental facility model using Matlab

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Iraci Martinez; Moraes, Davi Almeida, E-mail: martinez@ipen.br, E-mail: dmoraes@dk8.com.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    The Fault Test Experimental Facility was developed to simulate a PWR nuclear power plant and is instrumented with temperature, level and pressure sensors. The Fault Test Experimental Facility can be operated to generate normal and fault data, and these failures can be added initially small, and their magnitude being increasing gradually. This work presents the Fault Test Experimental Facility model developed using the Matlab GUIDE (Graphical User Interface Development Environment) toolbox that consists of a set of functions designed to create interfaces in an easy and fast way. The system model is based on the mass and energy inventory balance equations. Physical as well as operational aspects are taken into consideration. The interface layout looks like a process flowchart and the user can set the input variables. Besides the normal operation conditions, there is the possibility to choose a faulty variable from a list. The program also allows the user to set the noise level for the input variables. Using the model, data were generated for different operational conditions, both under normal and fault conditions with different noise levels added to the input variables. Data generated by the model will be compared with Fault Test Experimental Facility data. The Fault Test Experimental Facility theoretical model results will be used for the development of a Monitoring and Fault Detection System. (author)

  10. Development of a fault test experimental facility model using Matlab

    International Nuclear Information System (INIS)

    Pereira, Iraci Martinez; Moraes, Davi Almeida

    2015-01-01

    The Fault Test Experimental Facility was developed to simulate a PWR nuclear power plant and is instrumented with temperature, level and pressure sensors. The Fault Test Experimental Facility can be operated to generate normal and fault data, and these failures can be added initially small, and their magnitude being increasing gradually. This work presents the Fault Test Experimental Facility model developed using the Matlab GUIDE (Graphical User Interface Development Environment) toolbox that consists of a set of functions designed to create interfaces in an easy and fast way. The system model is based on the mass and energy inventory balance equations. Physical as well as operational aspects are taken into consideration. The interface layout looks like a process flowchart and the user can set the input variables. Besides the normal operation conditions, there is the possibility to choose a faulty variable from a list. The program also allows the user to set the noise level for the input variables. Using the model, data were generated for different operational conditions, both under normal and fault conditions with different noise levels added to the input variables. Data generated by the model will be compared with Fault Test Experimental Facility data. The Fault Test Experimental Facility theoretical model results will be used for the development of a Monitoring and Fault Detection System. (author)

  11. Investigation of wax precipitation in crude oil: Experimental and modeling

    Directory of Open Access Journals (Sweden)

    Taraneh Jafari Behbahani

    2015-09-01

    Full Text Available In this work, a series of experiments were carried to investigation of rheological behavior of crude oil using waxy crude oil sample in the absence/presence of flow improver such as ethylene-vinyl acetate copolymer. The rheological data covered the temperature range of 5–30 °C. The results indicated that the performance of flow improver was dependent on its molecular weight. Addition of small quantities of flow improver, can improve viscosity and pour point of crude oil. Also, an Artificial Neural Network (ANN model using Multi-Layer Perceptron (MLP topology has been developed to account wax appearance temperature and the amount of precipitated wax and the model was verified using experimental data given in this work and reported in the literature. In order to compare the performance of the proposed model based on Artificial Neural Network, the wax precipitation experimental data at different temperatures were predicted using solid solution model and multi-solid phase model. The results showed that the developed model based on Artificial Neural Network can predict more accurately the wax precipitation experimental data in comparison to the previous models such as solid solution and multi-solid phase model with AADs less than 0.5%. Furthermore, the number of parameters required for the Artificial Neural Network (ANN model is less than the studied thermodynamic models.

  12. Optimality models in the age of experimental evolution and genomics

    OpenAIRE

    Bull, J. J.; Wang, I.-N.

    2010-01-01

    Optimality models have been used to predict evolution of many properties of organisms. They typically neglect genetic details, whether by necessity or design. This omission is a common source of criticism, and although this limitation of optimality is widely acknowledged, it has mostly been defended rather than evaluated for its impact. Experimental adaptation of model organisms provides a new arena for testing optimality models and for simultaneously integrating genetics. First, an experimen...

  13. Confrontation of thermoluminescence models in lithium fluoride with experimental data

    International Nuclear Information System (INIS)

    Niewiadomski, T.

    1976-12-01

    The thermoluminescent properties of lithium fluoride depend on numerous factors and are much more complex than those of other phosphors. The so far developed fragmentary models are meant to explain the relationships between crystal defect structure and the processes involved in TL. An attempt has been made to compare these models with the veryfied experimental data and to point out the observations which are inconsistant with the models. (author)

  14. Mechanical Recanalization of Cerebral Artery Embolic Occlusion Using a Self-Expanding Stent: Experimental Analysis in Canine Model

    International Nuclear Information System (INIS)

    Choi, Jin Woo; Kim, Snag Joon; Lee, Deok Hee; Suh, Dae Chul

    2011-01-01

    To evaluate the feasibility of a self-expanding stent for acute embolic occlusion, and recanalization mechanism by histologic examination. Five mongrel dogs were used as study subjects. Each vertebral artery was occluded, and a self-expanding stent was used for recanalization. We evaluated the technical success rate for the placement of the stent to the targeted vessel, the recanalization rate, and residual stenosis. We obtained two specimens of the stented vertebral arteries for histologic evaluation. One dog died of an unknown cause during the induction of anesthesia. In two dogs, only one side of the vertebral artery was used, whereas both vertebral arteries were used in the remaining dogs. A total of six vertebral arteries were successfully occluded. The technical success rate for stenting without complication was 66.7%. The immediate recanalization rate after stenting was 100%. The residual stenosis was 35.6 ± 18.6%. On microscopic examination, the stent concentrically displaced the clot and the clot was captured between the stent mesh and arterial wall. Self-expanding stents were effective in revascularizing the cerebrovascular embolic occlusion. The self-expanding stent seemed to achieve recanalization by pushing the clot to the arterial wall and capturing the clot between the stent mesh and arterial wall.

  15. Mechanical Recanalization of Cerebral Artery Embolic Occlusion Using a Self-Expanding Stent: Experimental Analysis in Canine Model

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jin Woo; Kim, Snag Joon; Lee, Deok Hee; Suh, Dae Chul [Dept. of Radiology and Research Institute of Radiology, Asan Medical Center, Ulsan University College of Medicine, Seoul (Korea, Republic of)

    2011-07-15

    To evaluate the feasibility of a self-expanding stent for acute embolic occlusion, and recanalization mechanism by histologic examination. Five mongrel dogs were used as study subjects. Each vertebral artery was occluded, and a self-expanding stent was used for recanalization. We evaluated the technical success rate for the placement of the stent to the targeted vessel, the recanalization rate, and residual stenosis. We obtained two specimens of the stented vertebral arteries for histologic evaluation. One dog died of an unknown cause during the induction of anesthesia. In two dogs, only one side of the vertebral artery was used, whereas both vertebral arteries were used in the remaining dogs. A total of six vertebral arteries were successfully occluded. The technical success rate for stenting without complication was 66.7%. The immediate recanalization rate after stenting was 100%. The residual stenosis was 35.6 {+-} 18.6%. On microscopic examination, the stent concentrically displaced the clot and the clot was captured between the stent mesh and arterial wall. Self-expanding stents were effective in revascularizing the cerebrovascular embolic occlusion. The self-expanding stent seemed to achieve recanalization by pushing the clot to the arterial wall and capturing the clot between the stent mesh and arterial wall.

  16. Myocardial Blood Volume Is Associated with Myocardial Oxygen Consumption: An Experimental Study with CMR in a Canine Model

    Science.gov (United States)

    McCommis, Kyle S.; Zhang, Haosen; Goldstein, Thomas A.; Misselwitz, Bernd; Abendschein, Dana R.; Gropler, Robert J.; Zheng, Jie

    2009-01-01

    OBJECTIVES To evaluate the feasibility of cardiovascular MR (CMR) to determine regional myocardial perfusion and O2 metabolism, and assess the role of myocardial blood volume (MBV) on oxygen supply. BACKGROUND Coronary artery disease presents as an imbalance of myocardial oxygen supply and demand. We have developed relevant CMR methods to determine the relationship of myocardial blood flow (MBF) and MBV to oxygen consumption (MVO2) during pharmacologic hyperemia. METHODS Twenty-one mongrel dogs were studied with varying stenosis severities imposed on the proximal left anterior descending (LAD) coronary artery. MBF and MBV were determined by CMR first-pass perfusion, while the oxygen extraction fraction (OEF) and MVO2 were determined by the myocardial Blood-Oxygen-Level-Dependent (BOLD) effect and Fick’s law, respectively. MR imaging was performed at rest, and during either dipyridamole-induced vasodilation or dobutamine-induced hyperemia. Regional differences in myocardial perfusion and oxygenation were then evaluated. RESULTS Dipyridamole and dobutamine both led to 145–200% increases in MBF and 50–80% increases in MBV in normal perfused myocardium. As expected, MVO2 increased more significantly with dobutamine (~175%) than dipyridamole (~40%). Coronary stenosis resulted in an attenuation of MBF, MBV, and MVO2 in both the LAD-subtended stenosis region and the left circumflex subtended remote region. Liner regression analysis showed that MBV reserve appears to be more correlated with MVO2 reserve during dobutamine stress than MBF reserve, particularly in the stenotic regions. Conversely, MBF reserve appears to be more correlated with MVO2 reserve during dipyridamole, although neither of these differences was significant. CONCLUSIONS Noninvasive evaluation of both myocardial perfusion and oxygenation by CMR facilitates direct monitoring of regional myocardial ischemia and provides a valuable tool for better understanding microvascular pathophysiology. These techniques could complement delayed enhancement and wall motion analysis protocols, making MRI a valuable “one-stop shop” for imaging of myocardial ischemia. PMID:19909936

  17. Experimental Validation of a Dynamic Model for Lightweight Robots

    Directory of Open Access Journals (Sweden)

    Alessandro Gasparetto

    2013-03-01

    Full Text Available Nowadays, one of the main topics in robotics research is dynamic performance improvement by means of a lightening of the overall system structure. The effective motion and control of these lightweight robotic systems occurs with the use of suitable motion planning and control process. In order to do so, model-based approaches can be adopted by exploiting accurate dynamic models that take into account the inertial and elastic terms that are usually neglected in a heavy rigid link configuration. In this paper, an effective method for modelling spatial lightweight industrial robots based on an Equivalent Rigid Link System approach is considered from an experimental validation perspective. A dynamic simulator implementing the formulation is used and an experimental test-bench is set-up. Experimental tests are carried out with a benchmark L-shape mechanism.

  18. A sEMG model with experimentally based simulation parameters.

    Science.gov (United States)

    Wheeler, Katherine A; Shimada, Hiroshima; Kumar, Dinesh K; Arjunan, Sridhar P

    2010-01-01

    A differential, time-invariant, surface electromyogram (sEMG) model has been implemented. While it is based on existing EMG models, the novelty of this implementation is that it assigns more accurate distributions of variables to create realistic motor unit (MU) characteristics. Variables such as muscle fibre conduction velocity, jitter (the change in the interpulse interval between subsequent action potential firings) and motor unit size have been considered to follow normal distributions about an experimentally obtained mean. In addition, motor unit firing frequencies have been considered to have non-linear and type based distributions that are in accordance with experimental results. Motor unit recruitment thresholds have been considered to be related to the MU type. The model has been used to simulate single channel differential sEMG signals from voluntary, isometric contractions of the biceps brachii muscle. The model has been experimentally verified by conducting experiments on three subjects. Comparison between simulated signals and experimental recordings shows that the Root Mean Square (RMS) increases linearly with force in both cases. The simulated signals also show similar values and rates of change of RMS to the experimental signals.

  19. Experimental modeling of injectivity loss; Modelagem experimental da perda de injetividade

    Energy Technology Data Exchange (ETDEWEB)

    Bonato, Adriano Jose do Amaral Mello; Silva, Pedro Glauto de Farias e; Gomes, Vanessa Limeira Azevedo; Santos, Adriano dos [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil)

    2012-07-01

    Produced water reinjection, suspended particles are retained in the porous media causing formation damage and injectivity decline. In general the retention of the particles occurs near the side of injection, this fact occurs in most cases, due to the size exclusion. The modeling of filtration and the consequent formation damage is essential to the project management of water injection in oil reservoirs. Thus, mathematical models are studied to better predict the distribution of particles throughout the porous media and determine the parameters of adjustment to injectivity decline. Among these models, there is the classic model which consists in determining these parameters (coefficient of filtration and formation damage). The methodology used in modeling is given from the equations the mass conservation, kinetic particle retention, the modified Darcy equation and the function formation damage. This study aimed to improve experimental modeling, including development of software for acquisition and processing of experimental data, considering the variable number of pressure measurements along the sample. The software was developed using the Labview 2011 platform and allows the determination of relevant parameters to predict injectivity loss in water injection wells. Furthermore, based on the traditional model of filtration in porous media (including depth filtration and formation of the external plaster), the software was applied to predict injectivity loss in addition to the properties of the grout. Finally, the classical models for transporting suspensions and damage to the formation were observed. (author)

  20. Investigation of approximate models of experimental temperature characteristics of machines

    Science.gov (United States)

    Parfenov, I. V.; Polyakov, A. N.

    2018-05-01

    This work is devoted to the investigation of various approaches to the approximation of experimental data and the creation of simulation mathematical models of thermal processes in machines with the aim of finding ways to reduce the time of their field tests and reducing the temperature error of the treatments. The main methods of research which the authors used in this work are: the full-scale thermal testing of machines; realization of various approaches at approximation of experimental temperature characteristics of machine tools by polynomial models; analysis and evaluation of modelling results (model quality) of the temperature characteristics of machines and their derivatives up to the third order in time. As a result of the performed researches, rational methods, type, parameters and complexity of simulation mathematical models of thermal processes in machine tools are proposed.

  1. Alkaline phosphatase activity in gingival crevicular fluid during canine retraction.

    Science.gov (United States)

    Batra, P; Kharbanda, Op; Duggal, R; Singh, N; Parkash, H

    2006-02-01

    The aim of the study was to investigate alkaline phosphatase activity in the gingival crevicular fluid (GCF) during orthodontic tooth movement in humans. Postgraduate orthodontic clinic. Ten female patients requiring all first premolar extractions were selected and treated with standard edgewise mechanotherapy. Canine retraction was done using 100 g sentalloy springs. Maxillary canine on one side acted as experimental site while the contralateral canine acted as control. Gingival crevicular fluid was collected from mesial and distal of canines before initiation of canine retraction (baseline), immediately after initiation of retraction, and on 1st, 7th, 14th and 21st day and the alkaline phosphatase activity was estimated. The results show significant (p < 0.05) changes in alkaline phosphatase activity on the 7th, 14th and 21st day on both mesial and distal aspects of the compared experimental and control sides. The peak in enzyme activity occurred on the 14th day of initiation of retraction followed by a significant fall in activity especially on the mesial aspect. The study showed that alkaline phosphatase activity could be successfully estimated in the GCF using calorimetric estimation assay kits. The enzyme activity showed variation according to the amount of tooth movement.

  2. Contact Modelling in Resistance Welding, Part II: Experimental Validation

    DEFF Research Database (Denmark)

    Song, Quanfeng; Zhang, Wenqi; Bay, Niels

    2006-01-01

    Contact algorithms in resistance welding presented in the previous paper are experimentally validated in the present paper. In order to verify the mechanical contact algorithm, two types of experiments, i.e. sandwich upsetting of circular, cylindrical specimens and compression tests of discs...... with a solid ring projection towards a flat ring, are carried out at room temperature. The complete algorithm, involving not only the mechanical model but also the thermal and electrical models, is validated by projection welding experiments. The experimental results are in satisfactory agreement...

  3. Particle deposition in human and canine tracheobronchial casts: Annual progress report

    International Nuclear Information System (INIS)

    Cohen, B.S.

    1987-01-01

    This work measures deposition patterns and efficiencies of aerosols within realistic, physical models of the tracheobronchial airways of humans and experimental animals over a range of particle sizes from 0.01 to 1.0 μm, for a variety of respiratory modes and rates. Full morphometric and flow distribution measurements were completed on casts of human and canine tracheobronchial airways, which extend from just below the larynx to airways 1 mm in diameter. They show basic similarities in the distribution of airflow, but also species differences which must be considered. The distribution of airflow was measured for minute volumes equivalent to 6, 11, 17 and 22 L min -1 for the human and 3, 6, 8 and 11 L min -1 for the canine for both constant and pulsatile inspiratory flow. Inertance was found to carry more of the flow to airways of the lower lobes at higher flow rates. Basic differences in airway branching pattern result in a more distinct change in airflow distribution as flow rate changes for the canine cast as compared with the human cast. These differences will contribute to differing patterns of mass transfer of inhaled particles in central airways of the two species. 8 refs., 2 figs., 5 tabs

  4. Optimality models in the age of experimental evolution and genomics.

    Science.gov (United States)

    Bull, J J; Wang, I-N

    2010-09-01

    Optimality models have been used to predict evolution of many properties of organisms. They typically neglect genetic details, whether by necessity or design. This omission is a common source of criticism, and although this limitation of optimality is widely acknowledged, it has mostly been defended rather than evaluated for its impact. Experimental adaptation of model organisms provides a new arena for testing optimality models and for simultaneously integrating genetics. First, an experimental context with a well-researched organism allows dissection of the evolutionary process to identify causes of model failure--whether the model is wrong about genetics or selection. Second, optimality models provide a meaningful context for the process and mechanics of evolution, and thus may be used to elicit realistic genetic bases of adaptation--an especially useful augmentation to well-researched genetic systems. A few studies of microbes have begun to pioneer this new direction. Incompatibility between the assumed and actual genetics has been demonstrated to be the cause of model failure in some cases. More interestingly, evolution at the phenotypic level has sometimes matched prediction even though the adaptive mutations defy mechanisms established by decades of classic genetic studies. Integration of experimental evolutionary tests with genetics heralds a new wave for optimality models and their extensions that does not merely emphasize the forces driving evolution.

  5. Comparison of a novel bone-tendon allograft with a human dermis-derived patch for repair of chronic large rotator cuff tears using a canine model.

    Science.gov (United States)

    Smith, Matthew J; Cook, James L; Kuroki, Keiichi; Jayabalan, Prakash S; Cook, Cristi R; Pfeiffer, Ferris M; Waters, Nicole P

    2012-02-01

    This study tested a bone-tendon allograft versus human dermis patch for reconstructing chronic rotator cuff repair by use of a canine model. Mature research dogs (N = 15) were used. Radiopaque wire was placed in the infraspinatus tendon (IST) before its transection. Three weeks later, radiographs showed IST retraction. Each dog then underwent 1 IST treatment: debridement (D), direct repair of IST to bone with a suture bridge and human dermis patch augmentation (GJ), or bone-tendon allograft (BT) reconstruction. Outcome measures included lameness grading, radiographs, and ultrasonographic assessment. Dogs were killed 6 months after surgery and both shoulders assessed biomechanically and histologically. BT dogs were significantly (P = .01) less lame than the other groups. BT dogs had superior bone-tendon, tendon, and tendon-muscle integrity compared with D and GJ dogs. Biomechanical testing showed that the D group had significantly (P = .05) more elongation than the other groups whereas BT had stiffness and elongation characteristics that most closely matched normal controls. Radiographically, D and GJ dogs showed significantly more retraction than BT dogs (P = .003 and P = .045, respectively) Histologically, GJ dogs had lymphoplasmacytic infiltrates, tendon degeneration and hypocellularity, and poor tendon-bone integration. BT dogs showed complete incorporation of allograft bone into host bone, normal bone-tendon junctions, and well-integrated allograft tendon. The bone-tendon allograft technique re-establishes a functional IST bone-tendon-muscle unit and maintains integrity of repair in this model. Clinical trials using this bone-tendon allograft technique are warranted. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  6. Radiation, chemotherapy and surgery for canine osteosarcoma

    International Nuclear Information System (INIS)

    Powers, B.E.; Withrow, S.J.; La Rue, S.M.; Straw, R.C.; Gillette, E.L.

    1987-01-01

    Spontaneous canine osteosarcomas is an excellent model for of human osterosarcoma. Twenty dogs with obsteorsarcoma were treated with intravenous or intraarterial cisplatin with or without radiation therapy. This treatment was given 3 weeks prior to limb sparing surgery involving excision of the tumor and allograft replacement. The excised tumor specimen was examined for complete removal and percentage of necrotic tumor measured by planimetry. Intraveneous and intraarterial cisplatin and radiation methods were compared. Data discussing rate of disease development and recurrences is given

  7. Bilateral supernumerary primary maxillary canines

    Directory of Open Access Journals (Sweden)

    Santanu Mukhopadhyay

    2018-01-01

    Full Text Available Supernumerary teeth are more common in the permanent than in primary dentition. In the primary dentition, the anomaly is most frequently observed in the maxillary lateral incisor region, followed by the maxillary midline where they are termed as mesiodens. Supernumerary teeth in the primary canine region are rare. This paper describes a rare case of nonsyndromic supernumerary primary maxillary canine distributed bilaterally in a 4-year-old boy. Both the supernumeraries resembled size and shape of normal primary canine. The right supplemental canine is high labially placed, whereas the left one is seen normally aligned in the dental arch distal to lateral incisor. One of the most significant sequelae of primary supernumerary teeth is their duplication in the permanent series. Radiographic examination of supernumerary primary canine did not indicate any such anomaly in the permanent dentition. The patient was kept under observation.

  8. Team Modelling: Review of Experimental Scenarios and Computational Models

    Science.gov (United States)

    2006-09-01

    les auteurs ont réuni et examiné des scénarios ayant servi dans le cadre d’études antérieures sur les équipes, ils ont développé d’importants...cognition, perception, sensation, motor action and knowledge, that embody a principled underlying theory or framework for human information...Processing) integrates Qinetiq’s (POP) model with DRDC’s IP/PCT (Perceptual Control Theory ) models. In particular, the POP/IP model includes the

  9. Initial study of sediment antagonism and characteristics of silver nanoparticle-coated biliary stents in an experimental animal model.

    Science.gov (United States)

    Tian, Yigeng; Xia, Mingfeng; Zhang, Shuai; Fu, Zhen; Wen, Qingbin; Liu, Feng; Xu, Zongzhen; Li, Tao; Tian, Hu

    2016-01-01

    Plastic biliary stents used to relieve obstructive jaundice are frequently blocked by sediment, resulting in loss of drainage. We prepared stents coated with silver nanoparticles (AgNPs) and compared their ability to resist sedimentation with Teflon stents in a beagle model of obstructive jaundice. AgNP-coated Teflon biliary stents were prepared by chemical oxidation-reduction and evaluated in an obstructive jaundice model that was produced by ligation of common bile duct (CBD); animals were randomized to two equal groups for placement of AgNP-coated or Teflon control stents. Liver function and inflammatory index were found to be similar in the two groups, and the obstruction was relieved. Stents were removed 21 days after insertion and observed by scanning and transmission electron microscopy. The AgNP coating was analyzed by energy dispersive X-ray analysis (EDXA), and the composition of sediment was assayed by Fourier-transform infrared (FTIR) spectroscopy. Electron microscopy revealed a black, closely adherent AgNP stent coating, with thicknesses of 1.5-6 µm. Sediment thickness and density were greater on Teflon than on AgNP-coated stents. EDXA confirmed the stability and integrity of the AgNP coating before and after in vivo animal experimentation. FTIR spectroscopy identified stent sediment components including bilirubin, cholesterol, bile acid, protein, calcium, and other substances. AgNP-coated biliary stents resisted sediment accumulation in this canine model of obstructive jaundice caused by ligation of the CBD.

  10. Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma.

    Science.gov (United States)

    von Euler, Henrik; Sadeghi, Arian; Carlsson, Björn; Rivera, Patricio; Loskog, Angelica; Segall, Thomas; Korsgren, Olle; Tötterman, Thomas H

    2008-05-01

    Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.

  11. Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior

    Directory of Open Access Journals (Sweden)

    Abadie Jerome

    2011-05-01

    Full Text Available Abstract Background Histiocytic malignancies in both humans and dogs are rare and poorly understood. While canine histiocytic sarcoma (HS is uncommon in the general domestic dog population, there is a strikingly high incidence in a subset of breeds, suggesting heritable predisposition. Molecular cytogenetic profiling of canine HS in these breeds would serve to reveal recurrent DNA copy number aberrations (CNAs that are breed and/or tumor associated, as well as defining those shared with human HS. This process would identify evolutionarily conserved cytogenetic changes to highlight regions of particular importance to HS biology. Methods Using genome wide array comparative genomic hybridization we assessed CNAs in 104 spontaneously occurring HS from two breeds of dog exhibiting a particularly elevated incidence of this tumor, the Bernese Mountain Dog and Flat-Coated Retriever. Recurrent CNAs were evaluated further by multicolor fluorescence in situ hybridization and loss of heterozygosity analyses. Statistical analyses were performed to identify CNAs associated with tumor location and breed. Results Almost all recurrent CNAs identified in this study were shared between the two breeds, suggesting that they are associated more with the cancer phenotype than with breed. A subset of recurrent genomic imbalances suggested involvement of known cancer associated genes in HS pathogenesis, including deletions of the tumor suppressor genes CDKN2A/B, RB1 and PTEN. A small number of aberrations were unique to each breed, implying that they may contribute to the major differences in tumor location evident in these two breeds. The most highly recurrent canine CNAs revealed in this study are evolutionarily conserved with those reported in human histiocytic proliferations, suggesting that human and dog HS share a conserved pathogenesis. Conclusions The breed associated clinical features and DNA copy number aberrations exhibited by canine HS offer a valuable model

  12. Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior

    International Nuclear Information System (INIS)

    Hedan, Benoit; Thomas, Rachael; Motsinger-Reif, Alison; Abadie, Jerome; Andre, Catherine; Cullen, John; Breen, Matthew

    2011-01-01

    Histiocytic malignancies in both humans and dogs are rare and poorly understood. While canine histiocytic sarcoma (HS) is uncommon in the general domestic dog population, there is a strikingly high incidence in a subset of breeds, suggesting heritable predisposition. Molecular cytogenetic profiling of canine HS in these breeds would serve to reveal recurrent DNA copy number aberrations (CNAs) that are breed and/or tumor associated, as well as defining those shared with human HS. This process would identify evolutionarily conserved cytogenetic changes to highlight regions of particular importance to HS biology. Using genome wide array comparative genomic hybridization we assessed CNAs in 104 spontaneously occurring HS from two breeds of dog exhibiting a particularly elevated incidence of this tumor, the Bernese Mountain Dog and Flat-Coated Retriever. Recurrent CNAs were evaluated further by multicolor fluorescence in situ hybridization and loss of heterozygosity analyses. Statistical analyses were performed to identify CNAs associated with tumor location and breed. Almost all recurrent CNAs identified in this study were shared between the two breeds, suggesting that they are associated more with the cancer phenotype than with breed. A subset of recurrent genomic imbalances suggested involvement of known cancer associated genes in HS pathogenesis, including deletions of the tumor suppressor genes CDKN2A/B, RB1 and PTEN. A small number of aberrations were unique to each breed, implying that they may contribute to the major differences in tumor location evident in these two breeds. The most highly recurrent canine CNAs revealed in this study are evolutionarily conserved with those reported in human histiocytic proliferations, suggesting that human and dog HS share a conserved pathogenesis. The breed associated clinical features and DNA copy number aberrations exhibited by canine HS offer a valuable model for the human counterpart, providing additional evidence towards

  13. Instrumental and ethical aspects of experimental research with animal models

    Directory of Open Access Journals (Sweden)

    Mirian Watanabe

    2014-02-01

    Full Text Available Experimental animal models offer possibilities of physiology knowledge, pathogenesis of disease and action of drugs that are directly related to quality nursing care. This integrative review describes the current state of the instrumental and ethical aspects of experimental research with animal models, including the main recommendations of ethics committees that focus on animal welfare and raises questions about the impact of their findings in nursing care. Data show that, in Brazil, the progress in ethics for the use of animals for scientific purposes was consolidated with Law No. 11.794/2008 establishing ethical procedures, attending health, genetic and experimental parameters. The application of ethics in handling of animals for scientific and educational purposes and obtaining consistent and quality data brings unquestionable contributions to the nurse, as they offer subsidies to relate pathophysiological mechanisms and the clinical aspect on the patient.

  14. The mechanics of buccal canine retraction springs for removable orthodontic appliances.

    Science.gov (United States)

    Waters, N E

    1982-07-01

    The force-displacement characteristics of three types of buccal-canine retraction spring to both horizontal (normal) and vertical displacements is derived from simple beam theory. The analyses are used to examine theoretically the effect of variations in the geometry of a given type of spring and also to compare the merits of three designs in terms of the force applied on activation, and their stability to vertical displacement. Experimental measurements on enlarged models of the force-displacement behaviour were in good agreement with the values predicted by the derived equations.

  15. Constitutive Model Calibration via Autonomous Multiaxial Experimentation (Postprint)

    Science.gov (United States)

    2016-09-17

    ABSTRACT (Maximum 200 words) Modern plasticity models contain numerous parameters that can be difficult and time consuming to fit using current...Abstract Modern plasticity models contain numerous parameters that can be difficult and time consuming to fit using current methods. Additional...complexity, is a difficult and time consuming process that has historically be a separate process from the experimental testing. As such, additional

  16. Experimental Analysis and Model Validation of an Opaque Ventilated Facade

    DEFF Research Database (Denmark)

    López, F. Peci; Jensen, Rasmus Lund; Heiselberg, Per

    2012-01-01

    Natural ventilation is a convenient way of reducing energy consumption in buildings. In this study an experimental module of an opaque ventilated façade (OVF) was built and tested for assessing its potential of supplying free ventilation and air preheating for the building. A numerical model was ...

  17. Capillary microreactors for lactic acid extraction: experimental and modelling study

    NARCIS (Netherlands)

    Susanti, Susanti; Winkelman, Jozef; Schuur, Boelo; Heeres, Hero; Yue, Jun

    2015-01-01

    Lactic acid is an important biobased chemical and, among others, is used for the production of poly-lactic acid. Down-stream processing using state of the art technology is energy intensive and leads to the formation of large amounts of salts. In this presentation, experimental and modeling studies

  18. Experimental data available for radiation damage modelling in reactor materials

    International Nuclear Information System (INIS)

    Wollenberger, H.

    Radiation damage modelling requires rate constants for production, annihilation and trapping of defects. The literature is reviewed with respect to experimental determination of such constants. Useful quantitative information exists only for Cu and Al. Special emphasis is given to the temperature dependence of the rate constants

  19. Low dose CT simulation using experimental noise model

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Satori; Zamyatin, Alexander A. [Toshiba Medical Systems Corporation, Tochigi, Otawarashi (Japan); Silver, Michael D. [Toshiba Medical Research Institute, Vernon Hills, IL (United States)

    2011-07-01

    We suggest a method to obtain system noise model experimentally without relying on assumptions on statistical distribution of the noise; also, knowledge of DAS gain and electronic noise level are not required. Evaluation with ultra-low dose CT data (5 mAs) shows good match between simulated and real data noise. (orig.)

  20. Novel sensors for food inspection modelling, fabrication and experimentation

    CERN Document Server

    Abdul Rahman, Mohd Syaifudin; Yu, Pak-Lam

    2014-01-01

    This book addresses presents recent developments of novel planar interdigital sensors for food inspection. It covers the fundamentals of sensors, their design, modelling and simulations, fabrications, characterizations, experimental investigations and analyses. This book will be useful for the engineers and researchers especially higher undergraduate, postgraduate students as well as practitioners working on the development of Electromagnetic Sensors.

  1. In a Canine Pneumonia Model of Exchange-Transfusion, Altering the Age but Not the Volume of Older Red Blood Cells Markedly Alters Outcome

    Science.gov (United States)

    Cortés-Puch, Irene; Remy, Kenneth E.; Solomon, Steven B.; Sun, Junfeng; Wang, Dong; Al-Hamad, Mariam; Kelly, Seth M.; Sinchar, Derek; Bellavia, Landon; Kanias, Tamir; Popovsky, Mark A.; Kim-Shapiro, Daniel B.; Klein, Harvey G.; Natanson, Charles

    2015-01-01

    Background Massive exchange-transfusion of 42-day-old red blood cells (RBCs) in a canine model of S. aureus pneumonia resulted in in vivo hemolysis with increases in cell-free hemoglobin (CFH), transferrin bound iron (TBI), non-transferrin bound iron (NTBI), and mortality. We have previously shown that washing 42-day-old RBCs before transfusion significantly decreased NTBI levels and mortality, but washing 7-day-old RBCs increased mortality and CFH levels. We now report the results of altering volume, washing, and age of RBCs. Study Design and Methods Two-year-old purpose-bred infected beagles were transfused with increasing volumes (5-10, 20-40, or 60-80 mL/kg) of either 42- or 7-day-old RBCs (n=36) or 80 mL/kg of either unwashed or washed RBCs with increasing storage age (14, 21, 28, or 35 days) (n=40). Results All volumes transfused (5-80 mL/kg) of 42-day-old RBCs, resulted in alike (i.e., not significantly different) increases in TBI during transfusion as well as in CFH, lung injury, and mortality rates after transfusion. Transfusion of 80 mL/kg of RBCs stored for 14, 21, 28 and 35 days resulted in increased CFH and NTBI in between levels found at 7 and 42 days of storage. However, washing RBCs of intermediate ages (14-35 days) does not alter NTBI and CFH levels or mortality rates. Conclusions Preclinical data suggest that any volume of 42-day-old blood potentially increases risks during established infection. In contrast, even massive volumes of 7-day-old blood result in minimal CFH and NTBI levels and risks. In contrast to the extremes of storage, washing blood stored for intermediate ages does not alter risks of transfusion or NTBI and CFH clearance. PMID:26469998

  2. Detection of viable myocardium in canine model with myocardial ischemia and ischemia-reperfusion by 125I-BMIPP: relation to regional blood flow

    International Nuclear Information System (INIS)

    Huang Gang; Zhao Huiyang; Shen Xuedong; Li Qing; Yuan Jimin; Zhu Cuiying

    1999-01-01

    Objective: The effects of BMIPP (β-methyl-iodophenyl pentadecanoic acid) on detecting viable myocardium and the relation between regional blood flow and the uptake of BMIPP were evaluated in canine model of myocardial ischemia and ischemia-reperfusion. Methods: 12 open-chest dogs under anesthesia were divided into two groups. Group I (ischemia group) had left circumflex coronary arterial occlusion for 2 h and group II (ischemia-reperfusion group) was occluded for 1 h and followed by 2 h reperfusion. Myocardial blood flow was measured with 99 Tc m -microspheres. 30 min after intravenous injection of 125 I-BMIPP and 99 Tc m -microspheres, the heart was excised rapidly and stained with Evans blue and NBT. Tissue samples (divided into approximately 1 g) of left ventricle were obtained, weighed and counted for 125 I and 99 Tc m . Regional blood flow and the uptake of BMIPP were expressed as percentages of average values in non-ischemic myocardium (two to three tissue samples) from the normal myocardium. Results: In ischemic myocardium (NBT positive samples), the uptake of BMIPP was relatively higher compared with regional blood flow [(67 +- 23)% vs (42 +- 19)%, P 0.05]. In ischemia-reperfusion group, regional blood flow was increased in ischemic and necrotic tissues, but the uptake of BMIPP was not enhanced with the increasing blood flow. Conclusions: BMIPP uptake seems to provide metabolic information independent of regional blood flow. The mismatching between regional blood flow and BMIPP uptake may indicate myocardial viability in the regions of hypoperfusion and the uptake of BMIPP in ischemic myocardium was related to existence of cellular metabolism

  3. Metabolic determinants of electrical failure in ex-vivo canine model of cardiac arrest: evidence for the protective role of inorganic pyrophosphate.

    Directory of Open Access Journals (Sweden)

    Junko Shibayama

    Full Text Available Deterioration of ventricular fibrillation (VF into asystole or severe bradycardia (electrical failure heralds a fatal outcome of cardiac arrest. The role of metabolism in the timing of electrical failure remains unknown.To determine metabolic factors of early electrical failure in an ex-vivo canine model of cardiac arrest (VF+global ischemia.Metabolomic screening was performed in left ventricular biopsies collected before and after 0.3, 2, 5, 10 and 20 min of VF and global ischemia. Electrical activity was monitored via plunge needle electrodes and pseudo-ECG. Four out of nine hearts exhibited electrical failure at 10.1±0.9 min (early-asys, while 5/9 hearts maintained VF for at least 19.7 min (late-asys. As compared to late-asys, early-asys hearts had more ADP, less phosphocreatine, and higher levels of lactate at some time points during VF/ischemia (all comparisons p<0.05. Pre-ischemic samples from late-asys hearts contained ∼25 times more inorganic pyrophosphate (PPi than early-asys hearts. A mechanistic role of PPi in cardioprotection was then tested by monitoring mitochondrial membrane potential (ΔΨ during 20 min of simulated-demand ischemia using potentiometric probe TMRM in rabbit adult ventricular myocytes incubated with PPi versus control group. Untreated myocytes experienced significant loss of ΔΨ while in the PPi-treated myocytes ΔΨ was relatively maintained throughout 20 min of simulated-demand ischemia as compared to control (p<0.05.High tissue level of PPi may prevent ΔΨm loss and electrical failure at the early phase of ischemic stress. The link between the two protective effects may involve decreased rates of mitochondrial ATP hydrolysis and lactate accumulation.

  4. Posterior cricoarytenoid muscle electrophysiologic changes are predictive of vocal cord paralysis with recurrent laryngeal nerve compressive injury in a canine model.

    Science.gov (United States)

    Puram, Sidharth V; Chow, Harold; Wu, Che-Wei; Heaton, James T; Kamani, Dipti; Gorti, Gautham; Chiang, Feng Yu; Dionigi, Gianlorenzo; Barczynski, Marcin; Schneider, Rick; Dralle, Henning; Lorenz, Kerstin; Randolph, Gregory W

    2016-12-01

    Injury to the recurrent laryngeal nerve (RLN) is a dreaded complication of endocrine surgery. Intraoperative neural monitoring (IONM) has been increasingly utilized to assess the functional status of the RLN. Although the posterior cricoarytenoid muscle (PCA) is innervated by the RLN as the abductor of the larynx, PCA electromyography (EMG) is infrequently recorded during IONM and PCA activity after RLN compressive injury remains poorly characterized. Single-subject prospective animal study. We employed a canine model to identify postcricoid EMG correlates of postoperative vocal cord paralysis (VCP). Postcricoid electrode recordings were obtained before and after compressive RLN injury associated with VCP. Normative postcricoid recordings revealed mean amplitude of 1288 microvolt (μV) and latency of 8.2 millisecond (ms) with maximum (1 milliamp [mA]) vagal stimulation, and mean amplitude of 1807 μV and latency of 3.5 ms with maximum (1 mA) RLN stimulation. Following injury that was associated with VCP, there was 62.1% decrement in postcricoid EMG amplitude with maximum vagal stimulation and 80% decrement with maximum RLN stimulation. Threshold stimulation of the vagus increased by 23%, and there was a corresponding 42% decrease in amplitude. For RLN stimulation, latency increased by 17.3% following injury, whereas threshold stimulation increased by 61% with 35.5% decrement in EMG amplitude. Thus, if RLN amplitude decreases by ≥ 80%, with absolute amplitude of ≤ 300 μV or less and latency increase of ≥ 10%, RLN injury is likely associated with VCP. Our results predict postoperative VCP based on postcricoid electromyographic IONM and may guide surgical decision making. NA Laryngoscope, 126:2744-2751, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  5. Comparison of the virulence of three H3N2 canine influenza virus isolates from Korea and China in mouse and Guinea pig models.

    Science.gov (United States)

    Xie, Xing; Na, Woonsung; Kang, Aram; Yeom, Minjoo; Yuk, Heejun; Moon, Hyoungjoon; Kim, Sung-Jae; Kim, Hyun-Woo; Kim, Jeong-Ki; Pang, Maoda; Wang, Yongshan; Liu, Yongjie; Song, Daesub

    2018-05-02

    Avian-origin H3N2 canine influenza virus (CIV) has been the most common subtype in Korea and China since 2007. Here, we compared the pathogenicity and transmissibility of three H3N2 CIV strains [Chinese CIV (JS/10), Korean CIV (KR/07), and Korean recombinant CIV between the classic H3N2 CIV and the pandemic H1N1 virus (MV/12)] in BALB/c mouse and guinea pig models. The pandemic H1N1 (CA/09) strain served as the control. BALB/c mice infected with H1N1 had high mortality and obvious body weight loss, whereas no overt disease symptoms were observed in mice inoculated with H3N2 CIV strains. The viral titers were higher in the group MV/12 than those in groups JS/10 and KR/07, while the mice infected with JS/10 showed higher viral titers in all tissues (except for the lung) than the mice infected with KR/07. The data obtained in guinea pigs also demonstrated that group MV/12 presented the highest loads in most of the tissues, followed by group JS/10 and KR/07. Also, direct contact transmissions of all the three CIV strains could be observed in guinea pigs, and for the inoculated and the contact groups, the viral titer of group MV/12 and KR/07 was higher than that of group JS/10 in nasal swabs. These findings indicated that the matrix (M) gene obtained from the pandemic H1N1 may enhance viral replication of classic H3N2 CIV; JS/10 has stronger viral replication ability in tissues as compared to KR/07, whereas KR/07 infected guinea pigs have more viral shedding than JS/10 infected guinea pigs. There exists a discrepancy in pathobiology among CIV isolates. Reverse genetics regarding the genomes of CIV isolates will be helpful to further explain the virus characteristics.

  6. A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model

    International Nuclear Information System (INIS)

    Fukumoto, Shinya; Hanazono, Kiwamu; Fu, Dah-Renn; Endo, Yoshifumi; Kadosawa, Tsuyoshi; Iwano, Hidetomo; Uchide, Tsuyoshi

    2013-01-01

    Highlights: •LAT1 is highly expressed in tumors but at low levels in normal tissues. •We examine LAT1 expression and function in malignant melanoma (MM). •LAT1 expression in MM tissues and cell lines is higher than those in normal tissues. •LAT1 selective inhibitors inhibit amino acid uptake and cell growth in MM cells. •New chemotherapeutic protocols including LAT1 inhibitors are effective for treatment. -- Abstract: L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for human malignant melanomas (MM) using canine spontaneous MM as a model for human MM. A comparative study of LAT expression was performed in 48 normal tissues, 25 MM tissues and five cell lines established from MM. The study observed LAT1 mRNA levels from MM tissues and cell lines that were significantly (P 3 H]L-Leucine uptake and cellular growth activities in CMeC-1 were inhibited in a dose-dependent manner by selective LAT1 inhibitors (2-amino-2-norbornane-carboxylic acid, BCH and melphalan, LPM). Inhibitory growth activities of various conventional anti-cancer drugs, including carboplatin, cyclophosphamide, dacarbazine, doxorubicin, mitoxantrone, nimustine, vinblastine and vincristine, were significantly (P < 0.05) enhanced by combination use with BCH or LPM. These findings suggest that LAT1 could be a new therapeutic target for MM

  7. Feasibility and Safety of Intra-arterial Pericyte Progenitor Cell Delivery Following Mannitol-Induced Transient Blood-Brain Barrier Opening in a Canine Model.

    Science.gov (United States)

    Youn, Sung Won; Jung, Keun-Hwa; Chu, Kon; Lee, Jong-Young; Lee, Soon-Tae; Bahn, Jae-jun; Park, Dong-Kyu; Yu, Jung-Suk; Kim, So-Yun; Kim, Manho; Lee, Sang Kun; Han, Moon-Hee; Roh, Jae-Kyu

    2015-01-01

    Stem cell therapy is currently being studied with a view to rescuing various neurological diseases. Such studies require not only the discovery of potent candidate cells but also the development of methods that allow optimal delivery of those candidates to the brain tissues. Given that the blood-brain barrier (BBB) precludes cells from entering the brain, the present study was designed to test whether hyperosmolar mannitol securely opens the BBB and enhances intra-arterial cell delivery. A noninjured normal canine model in which the BBB was presumed to be closed was used to evaluate the feasibility and safety of the tested protocol. Autologous adipose tissue-derived pericytes with platelet-derived growth factor receptor β positivity were utilized. Cells were administered 5 min after mannitol pretreatment using one of following techniques: (1) bolus injection of a concentrated suspension, (2) continuous infusion of a diluted suspension, or (3) bolus injection of a concentrated suspension that had been shaken by repeated syringe pumping. Animals administered a concentrated cell suspension without mannitol pretreatment served as a control group. Vital signs, blood parameters, neurologic status, and major artery patency were kept stable throughout the experiment and the 1-month posttreatment period. Although ischemic lesions were noted on magnetic resonance imaging in several mongrel dogs with concentrated cell suspension, the injection technique using repeated syringe shaking could avert this complication. The cells were detected in both ipsilateral and contralateral cortices and were more frequent at the ipsilateral and frontal locations, whereas very few cells were observed anywhere in the brain when mannitol was not preinjected. These data suggest that intra-arterial cell infusion with mannitol pretreatment is a feasible and safe therapeutic approach in stable brain diseases such as chronic stroke.

  8. Engraftment Efficiency after Intra-Bone Marrow versus Intravenous Transplantation of Bone Marrow Cells in a Canine Nonmyeloablative Dog Leukocyte Antigen-Identical Transplantation Model.

    Science.gov (United States)

    Lange, Sandra; Steder, Anne; Killian, Doreen; Knuebel, Gudrun; Sekora, Anett; Vogel, Heike; Lindner, Iris; Dunkelmann, Simone; Prall, Friedrich; Murua Escobar, Hugo; Freund, Mathias; Junghanss, Christian

    2017-02-01

    An intra-bone marrow (IBM) hematopoietic stem cell transplantation (HSCT) is assumed to optimize the homing process and therefore to improve engraftment as well as hematopoietic recovery compared with conventional i.v. HSCT. This study investigated the feasibility and efficacy of IBM HSCT after nonmyeloablative conditioning in an allogeneic canine HSCT model. Two study cohorts received IBM HSCT of either density gradient (IBM-I, n = 7) or buffy coat (IBM-II, n = 6) enriched bone marrow cells. An historical i.v. HSCT cohort served as control. Before allogeneic HSCT experiments were performed, we investigated the feasibility of IBM HSCT by using technetium-99m marked autologous grafts. Scintigraphic analyses confirmed that most IBM-injected autologous cells remained at the injection sites, independent of the applied volume. In addition, cell migration to other bones occurred. The enrichment process led to different allogeneic graft volumes (IBM-I, 2 × 5 mL; IBM-II, 2 × 25 mL) and significantly lower counts of total nucleated cells in IBM-I grafts compared with IBM-II grafts (1.6 × 10 8 /kg versus 3.8 × 10 8 /kg). After allogeneic HSCT, dogs of the IBM-I group showed a delayed engraftment with lower levels of donor chimerism when compared with IBM-II or to i.v. HSCT. Dogs of the IBM-II group tended to reveal slightly faster early leukocyte engraftment kinetics than intravenously transplanted animals. However, thrombocytopenia was significantly prolonged in both IBM groups when compared with i.v. HSCT. In conclusion, IBM HSCT is feasible in a nonmyeloablative HSCT setting but failed to significantly improve engraftment kinetics and hematopoietic recovery in comparison with conventional i.v. HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. Robust Bayesian Experimental Design for Conceptual Model Discrimination

    Science.gov (United States)

    Pham, H. V.; Tsai, F. T. C.

    2015-12-01

    A robust Bayesian optimal experimental design under uncertainty is presented to provide firm information for model discrimination, given the least number of pumping wells and observation wells. Firm information is the maximum information of a system can be guaranteed from an experimental design. The design is based on the Box-Hill expected entropy decrease (EED) before and after the experiment design and the Bayesian model averaging (BMA) framework. A max-min programming is introduced to choose the robust design that maximizes the minimal Box-Hill EED subject to that the highest expected posterior model probability satisfies a desired probability threshold. The EED is calculated by the Gauss-Hermite quadrature. The BMA method is used to predict future observations and to quantify future observation uncertainty arising from conceptual and parametric uncertainties in calculating EED. Monte Carlo approach is adopted to quantify the uncertainty in the posterior model probabilities. The optimal experimental design is tested by a synthetic 5-layer anisotropic confined aquifer. Nine conceptual groundwater models are constructed due to uncertain geological architecture and boundary condition. High-performance computing is used to enumerate all possible design solutions in order to identify the most plausible groundwater model. Results highlight the impacts of scedasticity in future observation data as well as uncertainty sources on potential pumping and observation locations.

  10. Systematic integration of experimental data and models in systems biology.

    Science.gov (United States)

    Li, Peter; Dada, Joseph O; Jameson, Daniel; Spasic, Irena; Swainston, Neil; Carroll, Kathleen; Dunn, Warwick; Khan, Farid; Malys, Naglis; Messiha, Hanan L; Simeonidis, Evangelos; Weichart, Dieter; Winder, Catherine; Wishart, Jill; Broomhead, David S; Goble, Carole A; Gaskell, Simon J; Kell, Douglas B; Westerhoff, Hans V; Mendes, Pedro; Paton, Norman W

    2010-11-29

    The behaviour of biological systems can be deduced from their mathematical models. However, multiple sources of data in diverse forms are required in the construction of a model in order to define its components and their biochemical reactions, and corresponding parameters. Automating the assembly and use of systems biology models is dependent upon data integration processes involving the interoperation of data and analytical resources. Taverna workflows have been developed for the automated assembly of quantitative parameterised metabolic networks in the Systems Biology Markup Language (SBML). A SBML model is built in a systematic fashion by the workflows which starts with the construction of a qualitative network using data from a MIRIAM-compliant genome-scale model of yeast metabolism. This is followed by parameterisation of the SBML model with experimental data from two repositories, the SABIO-RK enzyme kinetics database and a database of quantitative experimental results. The models are then calibrated and simulated in workflows that call out to COPASIWS, the web service interface to the COPASI software application for analysing biochemical networks. These systems biology workflows were evaluated for their ability to construct a parameterised model of yeast glycolysis. Distributed information about metabolic reactions that have been described to MIRIAM standards enables the automated assembly of quantitative systems biology models of metabolic networks based on user-defined criteria. Such data integration processes can be implemented as Taverna workflows to provide a rapid overview of the components and their relationships within a biochemical system.

  11. Waste glass corrosion modeling: Comparison with experimental results

    International Nuclear Information System (INIS)

    Bourcier, W.L.

    1994-01-01

    Models for borosilicate glass dissolution must account for the processes of (1) kinetically-controlled network dissolution, (2) precipitation of secondary phases, (3) ion exchange, (4) rate-limiting diffusive transport of silica through a hydrous surface reaction layer, and (5) specific glass surface interactions with dissolved cations and anions. Current long-term corrosion models for borosilicate glass employ a rate equation consistent with transition state theory embodied in a geochemical reaction-path modeling program that calculates aqueous phase speciation and mineral precipitation/dissolution. These models are currently under development. Future experimental and modeling work to better quantify the rate-controlling processes and validate these models are necessary before the models can be used in repository performance assessment calculations

  12. Clinical manifestations of canine distemper in Nigerian dogs ...

    African Journals Online (AJOL)

    Twenty dogs of local breeds found in Nigeria, experimentally infected with local isolate of canine distemper virus, manifested fever, conjunctivitis, photophobia salivation, anorexia, dermatitis, and diarrhoea. Apart from these clinical signs already described for the disease in other breeds of dogs,45% of the dogs showed ...

  13. Canine distemper associated with generalized oedema in Nigerian ...

    African Journals Online (AJOL)

    Twenty puppies of Nigeria local breed of dogs which were experimentally infected with a local isolate of canine distemper virus manifested clinical signs known for the disease including anorexia, ocular discharges, postular dermatitis on the lower abdomen and diarrhoea. In addition, they also manifested generalized ...

  14. Molecular characterization of the canine HMGB1.

    Science.gov (United States)

    Murua Escobar, H; Meyer, B; Richter, A; Becker, K; Flohr, A M; Bullerdiek, J; Nolte, I

    2003-01-01

    Due to the close similarities of numerous canine diseases to their human counterparts, the dog could join the mouse as the species of choice to unravel the genetic background of complex diseases as e.g. cancer and metabolic diseases. Accordingly, the role of the dog as a model for therapeutic approaches is strongly increasing. However, prerequisite for such studies is the characterization of the corresponding canine genes. Recently, the human high mobility group protein B1 (HMGB1) has attracted considerable interest of oncologists because of what is called its "double life". Besides its function as an architectural transcription factor HMGB1 can also be secreted by certain cells and then acts as a ligand for the receptor for advanced glycation end products (RAGE). The binding of HMGB1 to RAGE can activate key cell signaling pathways, such as p38(MAPK), JNK, and p42/p44(MAPK) emphasizing the important role of HMGB1 in inflammation and tumor metastasis. These results make HMGB1 a very interesting target for therapeutic studies done in model organisms like the dog. In this study we characterized the molecular structure of the canine HMGB1 gene on genomic and cDNA levels, its predicted protein, the gene locus and a basic expression pattern. Copyright 2003 S. Karger AG, Basel

  15. Modeling RERTR experimental fuel plates using the PLATE code

    International Nuclear Information System (INIS)

    Hayes, S.L.; Meyer, M.K.; Hofman, G.L.; Snelgrove, J.L.; Brazener, R.A.

    2003-01-01

    Modeling results using the PLATE dispersion fuel performance code are presented for the U-Mo/Al experimental fuel plates from the RERTR-1, -2, -3 and -5 irradiation tests. Agreement of the calculations with experimental data obtained in post-irradiation examinations of these fuels, where available, is shown to be good. Use of the code to perform a series of parametric evaluations highlights the sensitivity of U-Mo dispersion fuel performance to fabrication variables, especially fuel particle shape and size distributions. (author)

  16. Physics of human cooperation: experimental evidence and theoretical models

    Science.gov (United States)

    Sánchez, Angel

    2018-02-01

    In recent years, many physicists have used evolutionary game theory combined with a complex systems perspective in an attempt to understand social phenomena and challenges. Prominent among such phenomena is the issue of the emergence and sustainability of cooperation in a networked world of selfish or self-focused individuals. The vast majority of research done by physicists on these questions is theoretical, and is almost always posed in terms of agent-based models. Unfortunately, more often than not such models ignore a number of facts that are well established experimentally, and are thus rendered irrelevant to actual social applications. I here summarize some of the facts that any realistic model should incorporate and take into account, discuss important aspects underlying the relation between theory and experiments, and discuss future directions for research based on the available experimental knowledge.

  17. Experimental, statistical, and biological models of radon carcinogenesis

    International Nuclear Information System (INIS)

    Cross, F.T.

    1991-09-01

    Risk models developed for underground miners have not been consistently validated in studies of populations exposed to indoor radon. Imprecision in risk estimates results principally from differences between exposures in mines as compared to domestic environments and from uncertainties about the interaction between cigarette-smoking and exposure to radon decay products. Uncertainties in extrapolating miner data to domestic exposures can be reduced by means of a broad-based health effects research program that addresses the interrelated issues of exposure, respiratory tract dose, carcinogenesis (molecular/cellular and animal studies, plus developing biological and statistical models), and the relationship of radon to smoking and other copollutant exposures. This article reviews experimental animal data on radon carcinogenesis observed primarily in rats at Pacific Northwest Laboratory. Recent experimental and mechanistic carcinogenesis models of exposures to radon, uranium ore dust, and cigarette smoke are presented with statistical analyses of animal data. 20 refs., 1 fig

  18. Development of experimental alloxan model of diabetes mellitus

    Directory of Open Access Journals (Sweden)

    V.V. Semenko

    2017-05-01

    Full Text Available Background. One of the main causes that lead to the disability of diabetic patients is diabetic retinopathy (DR. The relevance of the problem of DR necessitates the development of optimal experimental models on experimental animals to find effective ways of correcting this pathology. The purpose of our work was to develop an experimental alloxan model of type 1 diabetes mellitus (DM for the study of DR, which would not result in the lethal outcome of experimental animals under the action of alloxan; histological examination of changes in the tissues of the eyeball in the reproduction of the DM model for the selection of new effective methods for the metabolic treatment of DR in the early stages. Materials and methods. The experiment was carried out on white outbred Wistar rats weighing 180–200 g. The first group consisted of 20 animals that were not subjected to any influence, served as a control; second group — 30 animals, in which DM was modeled by administration of alloxan and fructose. Results. When modeling DR, vessel changes in the form of wall fibrosis, edema of the endothelium and vasospasm were found. There was also a decrease in the amount of pigment granules, dystrophic changes in the cells of the ganglionic layer and a layer of retinal rods and cones, which coincides with the descriptions of damage to the coats of the eyeball in patients with DM. Conclusions. In our studies, we have calculated the optimal dose of alloxan administration, which does not lead to the death of rats (the lethality of rats was absent and is an effective model not only of DM in general, but also of DR.

  19. The Effects of Orthodontic Forces during Canine Retraction Using Self-ligating Brackets on Gingival Crevicular Fluid Enzyme Activity, Canine Movement and Root Resorption

    International Nuclear Information System (INIS)

    Rohaya Megat Abdul Wahab; Albira Sintian; Zaidah Zainal Arifin; Zaidah Zainal Ariffin; Shahrul Hisham Zainal Ariffin

    2015-01-01

    Alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and aspartate aminotransferase (AST) activities were studied as bio markers of canine movement. Root resorption was also evaluated in canines subjected to the orthodontic forces. Nineteen subjects randomly received 100 and 150 g force using self-ligating brackets (SLB) either on the right or left site of maxillary arch. Gingival crevicular fluid samples were collected at distal sites of canines for five consecutive weeks. The activities of ALP, TRAP and AST were assayed and measured spectrophotometrically. Canine movement was measured for five consecutive weeks while root resorption was monitored at baseline, week 0 and week 5 using periapical radiographs. In 100 g group, TRAP activity significantly increased in week 3-5 when compared to TRAP baseline activity. However, ALP and AST activities slightly increased. In 150 g group, ALP and TRAP activities slightly increased when compared with their baseline activities. However, AST significantly increased in week 5. Canine movement and root resorption were not significantly different (p<0.05) in both groups. A force of 100 and 150 g slightly increased the bone modeling process and resulted in similar canine movement and root resorption. Therefore, 100 g force could be an optimum force for canine retraction and is preferable (compared with 150 g force) in canine retraction using SLB. (author)

  20. Experimental Evaluation of Equivalent-Fluid Models for Melamine Foam

    Science.gov (United States)

    Allen, Albert R.; Schiller, Noah H.

    2016-01-01

    Melamine foam is a soft porous material commonly used in noise control applications. Many models exist to represent porous materials at various levels of fidelity. This work focuses on rigid frame equivalent fluid models, which represent the foam as a fluid with a complex speed of sound and density. There are several empirical models available to determine these frequency dependent parameters based on an estimate of the material flow resistivity. Alternatively, these properties can be experimentally educed using an impedance tube setup. Since vibroacoustic models are generally sensitive to these properties, this paper assesses the accuracy of several empirical models relative to impedance tube measurements collected with melamine foam samples. Diffuse field sound absorption measurements collected using large test articles in a laboratory are also compared with absorption predictions determined using model-based and measured foam properties. Melamine foam slabs of various thicknesses are considered.

  1. Experimental validation of a Bayesian model of visual acuity.

    LENUS (Irish Health Repository)

    Dalimier, Eugénie

    2009-01-01

    Based on standard procedures used in optometry clinics, we compare measurements of visual acuity for 10 subjects (11 eyes tested) in the presence of natural ocular aberrations and different degrees of induced defocus, with the predictions given by a Bayesian model customized with aberrometric data of the eye. The absolute predictions of the model, without any adjustment, show good agreement with the experimental data, in terms of correlation and absolute error. The efficiency of the model is discussed in comparison with image quality metrics and other customized visual process models. An analysis of the importance and customization of each stage of the model is also given; it stresses the potential high predictive power from precise modeling of ocular and neural transfer functions.

  2. THE REDUCED CANINE PANCREAS TO STUDY THE EFFECTS OF INTRAOPERATIVE RADIOTHERAPY

    NARCIS (Netherlands)

    HEIJMANS, HJ; MEHTA, D; KLEIBEUKER, JH; SLUITER, WJ; HOEKSTRA, HJ

    1993-01-01

    A canine model is described to study the tolerance of the pancreas to intra-operative radiotherapy (IORT). The canine pancreas is a horseshoe-shaped organ. To create a homogeneous delivery of IORT to the whole pancreas surgical manipulation is necessary which may induce pancreatitis. A resection of

  3. Nd : YAG surgical laser effects in canine prostate tissue: temperature and damage distribution

    NARCIS (Netherlands)

    van Nimwegen, S. A.; L'Eplattenier, H. F.; Rem, A. I.; van der Lugt, J. J.; Kirpensteijn, J.

    2009-01-01

    An in vitro model was used to predict short-term, laser-induced, thermal damage in canine prostate tissue. Canine prostate tissue samples were equipped with thermocouple probes to measure tissue temperature at 3, 6, 9 and 12 mm depths. The tissue surface was irradiated with a Nd:YAG laser in contact

  4. Canine obesity: an overview.

    Science.gov (United States)

    Gossellin, J; Wren, J A; Sunderland, S J

    2007-08-01

    Canine patients are generally regarded as being clinically obese when their body weight is at least 15% above ideal. The incidence of obesity in dogs is thought to be in the range of 20-40% of the general population and, since obesity is known to predispose or exacerbate a range of serious medical conditions, its importance cannot be overstated. Management of obesity through dietary restriction and increased exercise is often difficult to achieve and dependent upon owner compliance. Until recently there has been no authorized therapeutic medication available for weight reduction in dogs, and drugs used in people have proved unsuitable. However, with the development of microsomal triglyceride transfer protein inhibitors for canine use, such as dirlotapide, the veterinarian has a novel method with which to augment traditional weight control programmes. This approach has the additional advantage that weight loss is achieved without dietary restriction or change in exercise regimen, providing encouragement for the owner to comply with subsequent dietary and exercise recommendations, thereby increasing the likelihood for long-term success.

  5. Peracute Infectious Canine Hepatitis

    Directory of Open Access Journals (Sweden)

    A. H. Cheema*, I. Ahmed, G. Mustafa and A. Aslam

    2012-05-01

    Full Text Available Peracute infectious canine hepatitis (ICH was diagnosed in two young male dogs out of 56 dead canines presented for necropsy examination during the period of April 2009 to June 2010. These dogs were purebred, one- month old Alsatian and 5-month old Labrador. None of the dogs had received any vaccination or deworming treatment; both had died after illness lasting for six hours and twenty four hours respectively. The dogs had shown signs of depression, anorexia and fever. At necropsy, lymph nodes were swollen, edematous and congested; livers were enlarged, bright red and mottled with numerous small white foci. Petechial hemorrhages were seen in the mucosa. Excessive serosanguinous fluid was present in the abdominal cavities. Histologically, the most significant lesion was necrohemorrhagic hepatitis with single cell necrosis of hepatocytes, lacunose dilation of sinusoids filled with blood and numerous large, solid intranuclear inclusion bodies (IIBs in the hepatocytes and macrophages. Both eosinophilic and basophilic (amphophilic inclusions were seen. It has been observed that ICH is re-emerging in some endemic countries. Pet dogs should be regularly protected by effective vaccination.

  6. Radioresistant canine hematopoietic cells

    International Nuclear Information System (INIS)

    Kawakami, T.G.; Shimizu, J.; Rosenblatt, L.S.; Goldman, M.

    1987-01-01

    Survival of dogs that are continuously exposed to a moderate dose-rate of gamma radiation (10 cGy/day) is dependent on the age of the dog at the time of exposure. Most dogs exposed postpartum to gamma radiation suffered from suppressed hematopoiesis and died of aplasia. On the other hand, none of the in utero-exposed dogs suffered from suppressed hematopoiesis and most became long-term survivors, tolerating 10-fold greater total dose, but dying of myeloproliferative disease (MPD). Using acute gamma irradiation of hematopoietic cells and colony forming unit cell assay (CFU), they observed that a canine hematopoietic cell line established from a myeloid leukemic dog that was a long-term survivor of continuous irradiation was approximately 4-fold more radioresistant than a hematopoietic cell line established from a dog with nonradiation-induced myeloid leukemia or hematopoietic cells from normal canine bone marrow. In utero dogs that are long-term survivors of continuous irradiation have radioresistant hematopoietic cells, and radioresistance that is a constitutive property of the cells

  7. Uterus transplantation: Experimental animal models and recent experience in humans

    Directory of Open Access Journals (Sweden)

    Sadık Şahin

    2015-03-01

    Full Text Available Uterus transplantation has been considered as an alternative management modality in the last few years for adoption or gestational surrogacy for women with absence of uterus due to congenital or acquired reasons. Surrogacy is legal in only a few countries because of ethical, social and legal issues. Up to date, a total of 11 uterus transplantation cases have been reported in which uteri were harvested from ten live donors and one donor with brain death. After unsuccessful attempt of first uterus transplantation, many studies have been conducted in animals and these experimental models enabled our knowledge to increase on this topic. First experimental studies were performed in rodents; later uterus transplantation was accomplished in sheep, pigs and rabbits. Recently, researches in non-human primates have led the experience regarding transplantation technique and success to improve. In this review, we reviewed the experimental animal researches in the area of uterus transplantation and recent experience in humans.

  8. The rabbit as an experimental model in laryngology

    Directory of Open Access Journals (Sweden)

    Carneiro, Christiano de Giacomo

    2009-06-01

    Full Text Available Introduction: In the research in laryngology we normally use animal models. The animal experimentation may also contribute largely for this evolution, mainly for the easy access compared to human larynxes and for they are more easily controlled. Objective: The objective of this work is to analyze the laryngofissure with vocal cords graft as an experimental surgical technique in male adult rabbits. Method: We studied 46 New Zealand albino rabbits submitted to microsurgery in both vocal cords with autologous unilateral or bilateral graft of fat or fascia. Results: There were 4 losses of 3 animals until the first week of the postoperative period and another after 19 days after surgery. In the subsequent animals there were no infection, hematoma or sutures dehiscence. Conclusion: The study enables the conclusion that the experimental laryngofissure in rabbits is a safe method that may be used for laryngological studies.

  9. Canine distemper virus-associated hypocalcemia.

    Science.gov (United States)

    Weisbrode, S E; Krakowka, S

    1979-01-01

    A retrospective study was done to correlate serum calcium concentrations and parathyroid gland ultrastructure to clinical, immunologic, and pathologic changes experimentally induced in gnotobiotic dogs by canine distemper virus (CDV). Dogs infected with CDV had significantly reduced serum calcium concentrations associated with ultrastructural evidence of parathyroid gland inactivity, degeneration, and viral inclusions. Although CDV-infected dogs exhibited neurologic signs, minimal lesions were present in the central nervous system. It is suggested that viral-induced parathyroid dysfunction may contribute to neutrologic disturbance of CDV infection.

  10. Genetic algorithms and experimental discrimination of SUSY models

    International Nuclear Information System (INIS)

    Allanach, B.C.; Quevedo, F.; Grellscheid, D.

    2004-01-01

    We introduce genetic algorithms as a means to estimate the accuracy required to discriminate among different models using experimental observables. We exemplify the technique in the context of the minimal supersymmetric standard model. If supersymmetric particles are discovered, models of supersymmetry breaking will be fit to the observed spectrum and it is beneficial to ask beforehand: what accuracy is required to always allow the discrimination of two particular models and which are the most important masses to observe? Each model predicts a bounded patch in the space of observables once unknown parameters are scanned over. The questions can be answered by minimising a 'distance' measure between the two hypersurfaces. We construct a distance measure that scales like a constant fraction of an observable, since that is how the experimental errors are expected to scale. Genetic algorithms, including concepts such as natural selection, fitness and mutations, provide a solution to the minimisation problem. We illustrate the efficiency of the method by comparing three different classes of string models for which the above questions could not be answered with previous techniques. The required accuracy is in the range accessible to the Large Hadron Collider (LHC) when combined with a future linear collider (LC) facility. The technique presented here can be applied to more general classes of models or observables. (author)

  11. Transvaginal ultrasound ovarian diathermy: sheep as an experimental model

    Directory of Open Access Journals (Sweden)

    Pimentel Anita M

    2012-01-01

    Full Text Available Abstract Background Some techniques of transvaginal ovarian drilling have been previously described. Nevertheless a monopolar transvaginal ovarian cauterization, that use the expertise and safety of transvaginal puncture for oocyte captation seems to be an easier and feasible approach. The aim of this study was to develop a minimally invasive ovarian cauterization technique under transvaginal ultrasound control, and to evaluate the safety of the transvaginal ovarian monopolar cauterization, female sheep at reproductive age were used as an experimental model. Findings An experimental study was performed in a university research center. Seventeen female sheep (15 Corriedale e 2 Suffolk in reproductive age were submitted to transvaginal ovarian cauterization with a monopolar Valleylab Force 2 electrocautery. Macroscopic and microscopic lesions were assessed. Ovarian size were 1.31 cm2 ± 0,43 (Corriedale and 3.41 cm2 ± 0,64 (Suffolk. From 30 ovaries from Corriedale sheep punctured, only 3 were cauterized, presenting macroscopic and typical microscopic lesion. In the Suffolk sheep group, only one ovary was cauterized. No lesion could be found in the needle path. Conclusions This is the first experimental animal model described for ovarian cauterization needle guided by transvaginal ultrasound. The sheep does not seem to be the ideal animal model to study this technique. Another animal model, whose ovaries are better identified by transvaginal ultrasound should be sought for this technique, theoretically less invasive, before it could be offered safely to women with polycystic ovary syndrome.

  12. Experimental designs for autoregressive models applied to industrial maintenance

    International Nuclear Information System (INIS)

    Amo-Salas, M.; López-Fidalgo, J.; Pedregal, D.J.

    2015-01-01

    Some time series applications require data which are either expensive or technically difficult to obtain. In such cases scheduling the points in time at which the information should be collected is of paramount importance in order to optimize the resources available. In this paper time series models are studied from a new perspective, consisting in the use of Optimal Experimental Design setup to obtain the best times to take measurements, with the principal aim of saving costs or discarding useless information. The model and the covariance function are expressed in an explicit form to apply the usual techniques of Optimal Experimental Design. Optimal designs for various approaches are computed and their efficiencies are compared. The methods working in an application of industrial maintenance of a critical piece of equipment at a petrochemical plant are shown. This simple model allows explicit calculations in order to show openly the procedure to find the correlation structure, needed for computing the optimal experimental design. In this sense the techniques used in this paper to compute optimal designs may be transferred to other situations following the ideas of the paper, but taking into account the increasing difficulty of the procedure for more complex models. - Highlights: • Optimal experimental design theory is applied to AR models to reduce costs. • The first observation has an important impact on any optimal design. • Either the lack of precision or small starting observations claim for large times. • Reasonable optimal times were obtained relaxing slightly the efficiency. • Optimal designs were computed in a predictive maintenance context

  13. A retrospective investigation on canine papillomavirus 1 (CPV1 in oral oncogenesis reveals dogs are not a suitable animal model for high-risk HPV-induced oral cancer.

    Directory of Open Access Journals (Sweden)

    Ilaria Porcellato

    Full Text Available CPV1 (also called COPV is a papillomavirus responsible for oral papillomatosis in young dogs. The involvement of this viral type in oral oncogenesis has been hypothesized in oral squamous cell carcinomas (SCCs, but has never been investigated in other neoplastic and hyperplastic oral lesions of dogs. Aim of this study was to investigate the presence of CPV1 in different neoplastic and hyperplastic lesions in order to assess its role in canine oral oncogenesis; according to the results obtained, a second aim of the study was to define if the dog can be considered a valid animal model for oral high risk HPV-induced tumors. Eighty-eight formalin-fixed, paraffin-embedded (FFPE canine oral lesions including 78 oral tumors (papillomas, SCCs, melanomas, ameloblastomas, oral adenocarcinomas and 10 hyperplastic lesions (gingival hyperplasia were investigated with immunohistochemistry for the presence of papillomavirus L1 protein and with Real-Time PCR for CPV1 DNA. RT-PCR for RNA was performed on selected samples. All viral papillomas tested were positive for immunohistochemistry and Real-time PCR. In 3/33 (10% SCCs, viral DNA was demonstrated but no viral RNA could be found. No positivity was observed both with immunohistochemistry and Real-Time PCR in the other hyperplastic and neoplastic lesions of the oral cavity of dogs. Even though the finding of CPV1 DNA in few SCCs in face of a negative immunohistochemistry could support the hypothesis of an abortive infection in the development of these lesions, the absence of viral RNA points out that CPV1 more likely represents an innocent bystander in SCC oncogenesis. The study demonstrates a strong association between CPV1 and oral viral papillomas whereas viral contribution to the pathogenesis of other oral lesions seems unlikely. Moreover, it suggests that a canine model of CPV1 infection for HPV-induced oncogenesis could be inappropriate.

  14. A retrospective investigation on canine papillomavirus 1 (CPV1) in oral oncogenesis reveals dogs are not a suitable animal model for high-risk HPV-induced oral cancer.

    Science.gov (United States)

    Porcellato, Ilaria; Brachelente, Chiara; Guelfi, Gabriella; Reginato, Alice; Sforna, Monica; Bongiovanni, Laura; Mechelli, Luca

    2014-01-01

    CPV1 (also called COPV) is a papillomavirus responsible for oral papillomatosis in young dogs. The involvement of this viral type in oral oncogenesis has been hypothesized in oral squamous cell carcinomas (SCCs), but has never been investigated in other neoplastic and hyperplastic oral lesions of dogs. Aim of this study was to investigate the presence of CPV1 in different neoplastic and hyperplastic lesions in order to assess its role in canine oral oncogenesis; according to the results obtained, a second aim of the study was to define if the dog can be considered a valid animal model for oral high risk HPV-induced tumors. Eighty-eight formalin-fixed, paraffin-embedded (FFPE) canine oral lesions including 78 oral tumors (papillomas, SCCs, melanomas, ameloblastomas, oral adenocarcinomas) and 10 hyperplastic lesions (gingival hyperplasia) were investigated with immunohistochemistry for the presence of papillomavirus L1 protein and with Real-Time PCR for CPV1 DNA. RT-PCR for RNA was performed on selected samples. All viral papillomas tested were positive for immunohistochemistry and Real-time PCR. In 3/33 (10%) SCCs, viral DNA was demonstrated but no viral RNA could be found. No positivity was observed both with immunohistochemistry and Real-Time PCR in the other hyperplastic and neoplastic lesions of the oral cavity of dogs. Even though the finding of CPV1 DNA in few SCCs in face of a negative immunohistochemistry could support the hypothesis of an abortive infection in the development of these lesions, the absence of viral RNA points out that CPV1 more likely represents an innocent bystander in SCC oncogenesis. The study demonstrates a strong association between CPV1 and oral viral papillomas whereas viral contribution to the pathogenesis of other oral lesions seems unlikely. Moreover, it suggests that a canine model of CPV1 infection for HPV-induced oncogenesis could be inappropriate.

  15. A compendium of canine normal tissue gene expression.

    Directory of Open Access Journals (Sweden)

    Joseph Briggs

    Full Text Available BACKGROUND: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. METHODOLOGY/PRINCIPAL FINDINGS: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of